Publications by authors named "Hamid Forootanfar"

60 Publications

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

J Biomater Appl 2021 Mar 15:8853282211001359. Epub 2021 Mar 15.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.
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http://dx.doi.org/10.1177/08853282211001359DOI Listing
March 2021

Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease.

Bioorg Chem 2021 Feb 19;110:104750. Epub 2021 Feb 19.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran; Biomaterials Group, Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran. Electronic address:

A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC = 9.8-0.71 µM) and showed remarkable BuChE inhibition activity (IC = 1.9-0.006 µM) compared with donepezil as the standard drug (IC = 0.023 and 3.4 µM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC = 0.71 µM) and BuChE (IC = 0.006 µM), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on HO- and Aβ-induced .neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
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http://dx.doi.org/10.1016/j.bioorg.2021.104750DOI Listing
February 2021

Chromone-lipoic acid conjugate: Neuroprotective agent having acceptable butyrylcholinesterase inhibition, antioxidant and copper-chelation activities.

Daru 2021 Jan 9. Epub 2021 Jan 9.

Biomaterials Group, Pharmaceutical Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran.

Purpose: Alzheimer's disease (AD) is a multifaceted neurodegenerative disease. To target simultaneously multiple pathological processes involved in AD, natural-origin compounds with unique characteristics are promising scaffolds to develop novel multi-target compounds in the treatment of different neurodegenerative disease, especially AD. In this study, novel chromone-lipoic acid hybrids were prepared to find a new multifunctional lead structure for the treatment of AD.

Methods: Chromone-lipoic acid hybrids were prepared through click reaction and their neuroprotection and anticholinesterase activity were fully evaluated. The anti-amyloid aggregation, antioxidant and metal-chelation activities of the best compound were also investigated by standard methods to find a new multi-functional agent against AD.

Results: The primary biological screening demonstrated that all compounds had significant neuroprotection activity against H2O2-induced cell damage in PC12 cells. Compound 19 as the most potent butyrylcholinesterase (BuChE) inhibitor (IC50 = 7.55 μM) having significant neuroprotection activity as level as reference drug was selected for further biological evaluations. Docking and kinetic studies revealed non-competitive mixed-type inhibition of BuChE by compound 19. It could significantly reduce formation of the intracellular reactive oxygen species (ROS) and showed excellent reducing power (85.57 mM Fe+2), comparable with quercetin and lipoic acid. It could also moderately inhibit Aβ aggregation and selectively chelate with copper ions in 2:1 M ratio.

Conclusion: Compound 19 could be considered as a hopeful multifunctional agent for the further development gainst AD owing to the acceptable neuroprotective and anti-BuChE activity, moderate anti-Aβ aggregation activity, outstanding antioxidant activity as well as selective copper chelation ability. A new chromone-lipoic acid hybrid was synthesized as anti-Alzheimer agent with BuChE inhibitory activity, anti-Aβ aggregation, metal-chelation and antioxidant properties.
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http://dx.doi.org/10.1007/s40199-020-00378-1DOI Listing
January 2021

Mono- and bis-pyrazolophthalazines: Design, synthesis, cytotoxic activity, DNA/HSA binding and molecular docking studies.

Bioorg Med Chem 2021 Jan 24;30:115944. Epub 2020 Dec 24.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Biomaterials Group, Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran. Electronic address:

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC > 200 µM) and excellent cytotoxic activity against A549 cell line with IC value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV-Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy.
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http://dx.doi.org/10.1016/j.bmc.2020.115944DOI Listing
January 2021

A facile one-step preparation of Ca(PO)(OH)/Li-BioMOFs resin nanocomposites with (licorice) root juice as green capping agent and mechanical properties study.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):1331-1339

Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran.

The Ca(PO)(OH)/Li-BioMOFs resin nanocomposites were prepared and introduced as a new dental resin nanocomposite. Ca(PO)(OH)/Li-BioMOFs resin nanocomposites were synthesized with individual mechanical properties in the presence of lecithin as a biostabilizer. The hydrothermal synthesis of hydroxyapatite (HAp) nanostructures occurred in the presence of (liquorice) root juice that acts not only as a green capping agent but also as a reductant compound with a high steric hindrance agent. Results showed that the mechanical properties of nano-Ca(PO)(OH) structures with a concentration of 60 ppm Li-BioMOF were increased by ∼132.5 MPa and 11.5 GPa for the flexural and Young's modulus, respectively. Based on the optical absorption ultraviolet-visible spectrum, the HAp nanocrystallites had a direct bandgap energy of 4.2 eV. The structural, morphological, and mechanical properties of the as-prepared nanoparticles were characterized with the FT-IR (Fourier-transform infra-red), UV-Vis (ultraviolet visible) spectrums, X-ray diffraction, SEM (scanning electron microscopy), and TEM (transmission electron microscopy) images, and atomic force microscopy (AFM). It is suggested that HAp structures loaded on the Li-BioMOFs are as a suitable and novel substrate which can be considered as a promising biomaterial in dental resin nanocomposites significantly improved the strength and modulus.
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http://dx.doi.org/10.1080/21691401.2020.1842748DOI Listing
December 2020

Lipase@zeolitic imidazolate framework ZIF-90: A highly stable and recyclable biocatalyst for the synthesis of fruity banana flavour.

Int J Biol Macromol 2021 Jan 6;166:1301-1311. Epub 2020 Nov 6.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran 1417614411, Iran. Electronic address:

A zeolitic imidazolate framework (ZIF-90) has been synthesized through solvothermal method. The structure was characterized by means of FT-IR spectroscopy, X-ray diffraction, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS). The synthesized ZIF-90 was applied as a support for immobilization of porcine pancreatic lipase (PPL). The immobilized enzyme (PPL@ZIF-90) exhibited immobilization yield and efficiency of 66 ± 1.8% and 89 ± 1.4%, respectively. The pH and thermal stability of PPL was improved after immobilization and the initial activity was retained at about 57% after 20 days of storage at 4 °C for PPL@ZIF-90. Moreover, about 57% of the original activity was remained following 10 cycles of application. In Michaelis-Menten kinetic studies, K value for PPL@ZIF-90 was lower, while, the V was higher than free PPL. Moreover, optimized conditions to produce fruity banana flavour upon esterification of butyric acid were investigated. The optimum esterification yield was 73.79 ± 1.31% in the presence of 245 mg PPL@ZIF-90, alcohol/acid ratio of 2.78 and 39 h reaction time. PPL@ZIF-90 showed 39% relative esterification yield after six cycles of reuse. The results suggested that PPL@ZIF-90 can be used as a potential effective biocatalyst for synthesis of isoamyl butyrate.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.011DOI Listing
January 2021

Immobilization of lipase on the modified magnetic diatomite earth for effective methyl esterification of isoamyl alcohol to synthesize banana flavor.

3 Biotech 2020 Oct 23;10(10):447. Epub 2020 Sep 23.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, 1417614411 Tehran, Iran.

The present study was designed to propose a simple, cost-effective, and efficient method for the preparation of a biocompatible composite made from magnetic diatomaceous earth (mDE) coated by aminopropyltriethoxysilane (APTES) and its application for immobilization of porcine pancreatic lipase (PPL). The produced mDE-APTES was instrumentally characterized and the obtained results of FTIR analysis and scanning electron microscopy equipped by energy-dispersive X-ray spectroscopy (SEM-EDS) showed successful coating of APTES on mDE surface. PPL was then immobilized onto mDE to obtain the biocatalyst of PPL@mDE (immobilization yield and efficiency of 78.0 ± 0.3% and 80.1 ± 0.6, respectively) and the presence of enzyme was confirmed by EDS method. The attained results of the reusability of PPL@mDE revealed that 57% of the initial activity was retained after 11 cycles of biocatalyst application. PPL@mDE demonstrated higher storage stability than the free enzyme at 4 °C, 25 °C, and 37 °C. The apparent (2.35 ± 0.12 mM) and (13.01 ± 0.64 µmol/min) values for the immobilized enzyme were considerably altered compared to those of the free enzyme ( > 0.05). PPL@mDE was subsequently employed for the synthesis of banana flavor (isoamyl acetate) in -hexane, which yields an esterification percentage of 100 at 37 °C after 3 h. However, it merits further investigations to find out about large-scale application of the as-synthesized biocatalyst for esterification.
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http://dx.doi.org/10.1007/s13205-020-02437-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511503PMC
October 2020

An organic solvent-tolerant lipase of MV1 with the potential application for enzymatic improvement of n6/n3 ratio in polyunsaturated fatty acids from fenugreek seed oil.

J Food Sci Technol 2020 Sep 17:1-12. Epub 2020 Sep 17.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, 1417614411 Tehran, Iran.

Lipase-catalyzed esterification is an efficient technique in the production of polyunsaturated fatty acid (PUFA) concentrates which are applied for nutrition and health purposes. In this project, a solvent-tolerant lipase from MV1 was immobilized and purified by a hydrophobic support. The purified lipase revealed enhanced activity and stability towards chemicals, organic solvents, and a broad range of pH values. The production of lipase was enhanced to 7.0 U/mL after optimization by a central composite design. Acylglycerols (AGs) rich in α-linolenic acid (45%, w/w) were produced and a favorable n-6/n-3 free fatty acid (FFA) ratio of 1.1 was achieved in fenugreek seed oil using the immobilized lipase. The ability of lipase in ester synthesis and the improvement of n6/n3 FFA ratio make it a suitable candidate in food production industries.
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http://dx.doi.org/10.1007/s13197-020-04784-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498116PMC
September 2020

Optimization of immobilization conditions of Bacillus atrophaeus FSHM2 lipase on maleic copolymer coated amine-modified graphene oxide nanosheets and its application for valeric acid esterification.

Int J Biol Macromol 2020 Nov 16;162:1790-1806. Epub 2020 Aug 16.

Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

The thermoalkalophilic lipase from Bacillus atrophaeus (BaL) was immobilized onto amine-functionalized graphene oxide nanosheets coated with the poly (maleic anhydride-alt-1-octadecene) copolymer (GO-NH-PMAO) and activated with glutaraldehyde as spacer arm through interfacial activation and subsequent multipoint covalent attachment. Experimental design method was applied for optimization of immobilization conditions including GO-NH-PMAO concentration, buffer concentration, pH, sonication time, enzyme concentration, glutaraldehyde concentration, time, and temperature. The optimum specific activity of the immobilized BaL (105.95 ± 2.37 U/mg) reached at 5 mg/mL for GO-NH-PMAO, 25 mM of buffer, pH 6.0, 60 min sonication time, 100 mM glutaraldehyde, 60 U/mL of enzyme, and 4 h of immobilization time at 25 °C, which was very close to the predicted amount (106.08 ± 1.42 U/mg). Maximum immobilization yield (81.35%) and efficiency (277.63%) were determined in optimal immobilization conditions. The obtained results clearly indicated that the immobilized BaL exhibited better stability at extreme temperature and pH than the free BaL. At temperature of 90 °C and pH 11, more than 90% of the initial activity of the immobilized BaL was retained. Furthermore, the immobilized BaL retained about 90% of its initial activity after 10 days of storage and 6 cycles of application. The esterification studies showed that maximum bioconversion of valeric acid to pentyl valerate using the free BaL (34.5%) and the immobilized BaL (96.3%) occurred in the xylene medium after 48 h of incubation at 60 °C. Therefore, the BaL immobilized on GO-NH-PMAO was introduced as an effective biocatalyst to synthesize green apple flavour ester.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.101DOI Listing
November 2020

New Strategies for Safe Cancer Therapy Using Electrospun Nanofibers: A Short Review.

Mini Rev Med Chem 2020 ;20(13):1272-1286

Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.

Electrospun nanofibers regarding their special features, including high drug loading capacity, high surface to volume area, flexibility, and ease of production and operation, are of great interest for being used in tissue engineering, and drug delivery approaches. In this context, several studies have been done for the production of biodegradable and biocompatible scaffolds containing different anticancer agents for fighting with solid tumors. Surprisingly, these scaffolds are able to deliver different combinations of drugs and agents, such as nanoparticles and release them in a time dependent manner. Here in this review, we summarize the principles of electrospinning and their uses in entrapment of drugs and anti-proliferative agents suitable for cancer therapy. The latest studies performed on treating cancer using electrospinning are mentioned and their advantages and disadvantages over conventional treatment methods are discussed.
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http://dx.doi.org/10.2174/1389557520666200513120924DOI Listing
April 2021

Regenerative medicine and drug delivery: Progress via electrospun biomaterials.

Mater Sci Eng C Mater Biol Appl 2020 Apr 6;109:110521. Epub 2019 Dec 6.

Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore. Electronic address:

Worldwide research on electrospinning enabled it as a versatile technique for producing nanofibers with specified physio-chemical characteristics suitable for diverse biomedical applications. In the case of tissue engineering and regenerative medicine, the nanofiber scaffolds' characteristics are custom designed based on the cells and tissues specific needs. This fabrication technique is also innovated for the production of nanofibers with special micro-structure and secondary structure characteristics such as porous fibers, hollow structure, and core- sheath structure. This review attempts to critically and succinctly capture the vast number of developments reported in the literature over the past two decades. We then discuss their applications as scaffolds for induction of cells growth and differentiation or as architecture for being used as graft for tissue engineering. The special nanofibers designed for improving regeneration of several tissues including heart, bone, central nerve system, spinal cord, skin and ocular tissue are introduced. We also discuss the potential of the electrospinning in drug delivery applications, which is a critical factor for cell culture, tissue formation and wound healing applications.
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http://dx.doi.org/10.1016/j.msec.2019.110521DOI Listing
April 2020

Efficient Keratinolysis of Poultry Feather Waste by the Halotolerant Keratinase from Salicola Marasensis.

Iran J Pharm Res 2019 ;18(4):1862-1870

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Sustainable development in the bio-treatment of large-scale biomass bulks requires high performance enzymes adapted to extreme conditions. An extracellular keratinolytic extract was obtained from the culture broth of a halotolerant strain of . Keratin hydrolyzing activity of the concentrated enzyme extract was observed on a 100 mg of pretreated feather waste. The concentrated enzyme was able to hydrolyze the poultry feathers by 25% after 12 h incubation. The bio-waste material was optimally hydrolyzed at pH 9 and temperature of 40 °C. Among reductants, 1,4-dithiothreitol, L-cysteine, 2-mercaptoethanol, glutathione, and sodium sulfate showed the most remarkable effect on the bio-waste keratinolysis, while the tested surfactants and urea had no significant effect on the keratinolytic activity. Hexane and hexadecane indicated strong effect on keratinase activity and bio-treatment in the presence of 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF]) as a hydrophobic ionic liquid resulted in a maximal of 80% extraction yield of soluble proteins from feathers. Considering the stability of the extracellular keratinolytic content in [BMIM][PF], the observed keratinase activity was noteworthy suggesting that the secreted enzyme may contribute to the bioconversion of feather wastes.
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http://dx.doi.org/10.22037/ijpr.2019.111710.13312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059026PMC
January 2019

Immobilization of Thermoalkalophilic Lipase from Bacillus atrophaeus FSHM2 on Amine-Modified Graphene Oxide Nanostructures: Statistical Optimization and Its Application for Pentyl Valerate Synthesis.

Appl Biochem Biotechnol 2020 Jun 10;191(2):579-604. Epub 2019 Dec 10.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Synthesis of (3-aminopropyl) triethoxysilane (APTES)-functionalized graphene oxide (GO) nanosheets, statistical optimization of conditions for immobilization of Bacillus atrophaeus lipase (BaL) on as-synthesized support, and application of the immobilized BaL for esterification of valeric acid were carried out in this investigation. The optimum specific activity of the immobilized BaL (81.60 ± 0.28 U mg) was achieved at 3 mg mL of GO-NH, 50 mM of phosphate buffer, pH 7.0, 60 min sonication time, 100 mM glutaraldehyde, 25 U mL of enzyme, and 8 h immobilization time at 4 °C. The immobilized BaL retained about 90% of its initial activity after 10 days of storage. Moreover, about 70% of the initial activity of the immobilized BaL was retained after 10 cycles of application. The results of esterification studies exhibited that maximum pentyl valerate synthesis using the free BaL (34.5%) and the immobilized BaL (92.7%) occurred in the organic solvent medium (xylene) after 48 h of incubation at 60 °C.
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http://dx.doi.org/10.1007/s12010-019-03180-1DOI Listing
June 2020

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Pak J Pharm Sci 2019 Sep;32(5):2167-2173

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 μg/mL and 6000 μg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 μg/mL and 1103±3.2 μg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.
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September 2019

Rapid and Facile Microwave-Assisted Synthesis of Palladium Nanoparticles and Evaluation of Their Antioxidant Properties and Cytotoxic Effects Against Fibroblast-Like (HSkMC) and Human Lung Carcinoma (A549) Cell Lines.

Biol Trace Elem Res 2020 Sep 28;197(1):132-140. Epub 2019 Nov 28.

Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran.

We report here a simple microwave irradiation method (850 W, 3 min) for the synthesis of palladium nanoparticles (Pd NPs) using ascorbic acid (as reducing agent) and sodium alginate (as stabilizer agent). The synthesized nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-Visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Antioxidant properties and cytotoxic effects of as-synthesized Pd NPs and Pd (II) acetate were also assessed. UV-Vis study showed the formation of Pd NPs with maximum absorption at 345 nm. From TEM analysis, it was observed that the Pd NPs had spherical shape with particle size distribution of 13-33 nm. Based on DPPH radical scavenging activity and reducing power assay, the antioxidant activities of Pd NPs were significantly higher than the Pd (II) acetate (p < 0.05). At the same concentration of 640 μg/mL, the scavenging activities were 32.9 ± 3.2% (Pd (II) acetate) and 27.2 ± 2.1% (Pd NPs). For A549 cells treated 48 h with Pd NPs, Pd (II) acetate, and cisplatin, the measured concentration necessary causing 50% cell death (IC) was 7.2 ± 1.7 μg/mL, 32.1 ± 2.1 μg/mL, and 206.2 ± 3.5 μg/mL, respectively. On HSkMC cells, the IC of the Pd NPs (320 μg/mL) was higher compared to Pd (II) acetate (228.7 ± 3.6 μg/mL), which confirmed lower cytotoxicity of the Pd NPs.
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http://dx.doi.org/10.1007/s12011-019-01984-0DOI Listing
September 2020

Antimicrobial, anti-biofilm, and anti-proliferative activities of lipopeptide biosurfactant produced by Acinetobacter junii B6.

Microb Pathog 2020 Jan 17;138:103806. Epub 2019 Oct 17.

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Lipopeptide biosurfactants (LPBs) are amphiphilic compounds produced by microorganisms exhibiting various biological activities. The main aim of the present study was to assess the in vitro antimicrobial, anti-biofilm, and cytotoxic effects of LPB produced by Acinetobacter junii (AjL). We determined AjL minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative bacteria as well as two fungal strains. Also, the anti-biofilm activity of AjL against the biofilm produced by clinically isolated bacterial strains was investigated. The AjL non-selectively showed activity against both Gram-positive and Gram-negative bacterial strains. The obtained results of the present study exhibited that the AjL in concentrations nearly below critical micelle concentration (CMC) has an effective antibacterial activity. It was found that the MIC values of AjL were lower than standard antifungal and it exhibited nearly 100% inhibition against Candida utilis. The attained results of the biofilm formation revealed that AjL disrupted the biofilm of Proteus mirabilis, Staphylococcus aureus, and Pseudomonas aeruginosa at 1250 μg/ml and 2500 μg/ml concentrations. The attained results of cytotoxic effect (determined by WST-1 assay) of the AjL revealed IC of 7.8 ± 0.4 mg/ml, 2.4 ± 0.5 mg/ml, and 5.7 ± 0.1 mg/ml, against U87, KB, and HUVEC cell lines, respectively. The results indicated that AjL has a potential application in the relatively new field of biomedicine.
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http://dx.doi.org/10.1016/j.micpath.2019.103806DOI Listing
January 2020

Folic acid decorated magnetic nanosponge: An efficient nanosystem for targeted curcumin delivery and magnetic resonance imaging.

J Colloid Interface Sci 2019 Nov 13;556:128-139. Epub 2019 Aug 13.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (FeO/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (FeO/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (FeO/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free FeO/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded FeO/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). FeO/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T MR signal intensity for FeO/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the FeO/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T MRI contrast efficiency.
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http://dx.doi.org/10.1016/j.jcis.2019.08.046DOI Listing
November 2019

Ondansetron enhanced diclofenac-induced nephrotoxicity in mice.

J Biochem Mol Toxicol 2019 Sep 23;33(9):e22378. Epub 2019 Jul 23.

Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

This study was performed to investigate the effect of ondansetron, a serotonin receptor (5-HT3) antagonist, in the alleviation of diclofenac-induced kidney injuries. NMRI mice were randomly divided into six groups and treated with (A) untreated control group, (B) diclofenac (100 mg/kg), (C) ondansetron (1 mg/kg), (D to F) ondansetron (0.1, 0.5, and 1 mg/kg, respectively) and diclofenac (100 mg/kg) for last 3 days of experiment. The oxidative stress tests strongly demonstrated the negative synergistic effects of diclofenac and ondansetron, regarding the observation of dose-dependent enhancement of malondialdehyde concentration, and reduction of glutathione content, and superoxide dismutase and catalase activity. Histopathological analyses revealed dose-dependent tubular epithelial cells degeneration, outstanding mononuclear cells infiltration, clear necrosis at the papillary region of kidney, dilation, and vascular hyperemia in mice kidney tissues treated with ondansetron and diclofenac. Conclusively, these findings suggested the possible ondansetron-diclofenac interaction through the induction of oxidative stress.
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http://dx.doi.org/10.1002/jbt.22378DOI Listing
September 2019

Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques.

Daru 2019 Dec 17;27(2):533-539. Epub 2019 Jul 17.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Background: Exosomes are natural nanoparticles that are involved in intercellular communication via transferring molecular information between cells. Recently, exosomes have been considered for exploitation as novel drug delivery systems due to their specific properties for carrying specific molecules and surface proteins.

Methods: In this study, U-87 cell derived exosomes have been investigated for delivery of a potent chemotherapeutic agent, paclitaxel (PTX). Two methods of loading were utilized to incorporate PTX in exosomes and the exosomes pharmaceutical and cytotoxic characterizations were determined.

Results: The drug loaded and empty exosomes were found to have particle size of 50-100 nm and zeta potential of ≈ - 20 mV. Loading capacity of 7.4 ng and 9.2 ng PTX into 1 μg of exosome total protein were also measured for incubation and sonication methods, respectively. Incorporation of PTX into exosomes significantly increased its cytotoxicity against U-87 cell line (59.92% cell viability) while it was found that the empty exosomes exhibited cell viability of 91.98%.

Conclusions: Loading method could affect the loading capacity of exosomes and their encapsulated chemotherapeutic molecule showed higher cytotoxicity into exosomes. These results promise exosomes as appropriate drug delivery system for glioblastoma multiform (GBM) treatment.
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http://dx.doi.org/10.1007/s40199-019-00280-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895332PMC
December 2019

Statistical optimization of cultural medium composition of thermoalkalophilic lipase produced by a chemically induced mutant strain of FSHM2.

3 Biotech 2019 Jul 15;9(7):268. Epub 2019 Jun 15.

2Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Extremophilic microbial derived lipases have been widely applied in different biotechnological processes due to their resistance to harsh conditions such as high salt concentration, elevated temperature, and extreme acidic or alkaline pH. The present study was designed to overproduce the halophilic, thermoalkalophilic lipase of FSHM2 through chemically induced random mutagenesis and optimization of cultural medium components assisted by statistical experimental design. At first, improvement of lipase production ability of FSHM2 was performed through exposure of the wild bacterial strain to ethidium bromide for 5-90 min to obtain a suitable mutant of lipase producer (designated as EB-5, 4301.1 U/l). Afterwards, Plackett-Burman experimental design augmented to D-optimal design was employed to optimize medium components (olive oil, maltose, glucose, sucrose, tryptone, urea, (NH)SO, NaCl, CaCl, and ZnSO) for lipase production by the EB-5 mutant. A maximum lipase production of 14,824.3 U/l was predicted in the optimum medium containing 5% of olive oil, 0.5% of glucose, 0.5% of sucrose, 2% of maltose, 2.5 g/l of yeast extract, 1.75 g/l of urea, 1.75 g/l of (NH)SO, 2.5 g/l of tryptone, 2 g/l of NaCl, 1 g/l of CaCl, and 1 g/l of ZnSO. A mean value of 14,773 ± 576.9 U/l of lipase was acquired from real experiments.
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http://dx.doi.org/10.1007/s13205-019-1789-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571094PMC
July 2019

Antimicrobial and anti-biofilm activities of Bi subnitrate and BiNPs produced by sp. SFG against clinical isolates of , , and .

IET Nanobiotechnol 2019 Jun;13(4):377-381

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.

In the present study sp. Shakibaie, Forootanfar, and Ghazanfari (SFG), was applied for preparation of biogenic Bi nanoparticles (BiNPs) and antibacterial and anti-biofilm activities of the purified BiNPs were investigated by microdilution and disc diffusion methods. Transmission electron micrographs showed that the produced nanostructures were spherical with a size range of 40-120 nm. The measured minimum inhibitory concentration of both the Bi subnitrate and BiNPs against three biofilms producing bacterial pathogens of , , and were found to be above 1280 µg/ml. Addition of BiNPs (1000 µg/disc) to antibiotic discs containing tobramycin, nalidixic acid, ceftriaxone, bacitracin, cefalexin, amoxicillin, and cefixime significantly increased the antibacterial effects against methicillin-resistant (MRSA) in comparison with Bi subnitrate ( < 0.05). Furthermore, the biogenic BiNPs decreased the biofilm formation of , , and to 55, 85, and 15%, respectively. In comparison to Bi subnitrate, BiNPs indicated significant anti-biofilm activity against ( < 0.05) while the anti-biofilm activity of BiNPs against and was similar to that of Bi subnitrate. To sum up, the attained results showed that combination of biogenic BiNPs with commonly used antibiotics relatively enhanced their antibacterial effects against MRSA.
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http://dx.doi.org/10.1049/iet-nbt.2018.5102DOI Listing
June 2019

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1846-1858

c Department of Pharmaceutical Biotechnology, Faculty of Pharmacy , Kerman University of Medical Sciences , Kerman , Iran.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.
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http://dx.doi.org/10.1080/21691401.2019.1611592DOI Listing
December 2019

Cytotoxicity investigations of biogenic tellurium nanorods towards PC12 cell line.

IET Nanobiotechnol 2018 Dec;12(8):1144-1149

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

The authors evaluated the cytotoxicity underlying mechanisms of biogenic tellurium (Te) nanorods (NRs) produced by the strain Te on the PC12 cell line. The half-maximal inhibitory concentration (IC) value was estimated at 5.05 ± 0.07 ng/ml for biogenic Te NRs and 2.44 ± 0.38 ng/ml for KTeO, respectively. The viability of PC12 was inhibited concentration dependent at doses of 1, 2.5, 5, 10, and 20 ng/ml. Te NRs principally induced late apoptosis or necrosis at IC concentration, without effect on caspase-3 activities. Furthermore, Te NRs reduced glutathione and enhanced malondialdehyde levels, and also reduced superoxide dismutase and catalase activities. These findings revealed that biogenic Te NRs were less toxic than KTeO. Additionally, they induced cytotoxity towards the PC12 cell line through the activation of late apoptosis independent of the caspase pathway, and may also enhance oxidative stress in the nervous system.
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http://dx.doi.org/10.1049/iet-nbt.2018.5137DOI Listing
December 2018

3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi-Target-Directed Ligands against Alzheimer's Disease.

Chem Biodivers 2019 May 8;16(5):e1800436. Epub 2019 Apr 8.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176, Iran.

Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC =0.27 μm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks β-amyloid (Aβ) self-aggregation with a ratio of 44.11 % at 100 μm and significantly protects PC12 cells from H O -damage in a dose-dependent manner.
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http://dx.doi.org/10.1002/cbdv.201800436DOI Listing
May 2019

Overproduction of thermoalkalophilic lipase secreted by Bacillus atrophaeus FSHM2 using UV-induced mutagenesis and statistical optimization of medium components.

Prep Biochem Biotechnol 2019 3;49(2):184-191. Epub 2019 Feb 3.

a Pharmaceutics Research Center, Institute of Neuropharmacology , Kerman University of Medical Sciences , Kerman , Iran.

Microbial enzymes of extremophilic origin serve as a vital source of stable industrial enzymes. The present study focused on overproduction of a thermoalkalophilic lipase produced by Bacillus atrophaeus FSHM2 through UV-induced random mutagenesis (5-45 min exposure to UV light) and factorial experimental design augmented to response surface methodology. Firstly, a UV-induced mutant (designated as UV-45) was developed after the exposure of wild strain to UV irradiation for 45 min which was able to secrete 3484.8 U/L lipase. Afterward, Plackett-Burman experimental approach augmented to central composite design was employed to optimize medium components (olive oil, maltose, glucose, sucrose, yeast extract, tryptone, urea, (NH)SO, NaCl, CaCl, and ZnSO) for lipase production by the UV-45 mutant strain. The maximum lipase production of 5505.3 U/L were predicted in medium containing 5% of olive oil, 0.69% of glucose, 0.69% of sucrose, 2.5% of maltose, yeast extract (0.7 g/L), urea (0.44 g/L), (NH)SO (2.44 g/L), tryptone (1.19 g/L), NaCl (1.61 g/L), CaCl (3.81 g/L), and ZnSO (1.42 g/L). A mean value of 5161.3 ± 83.3 U/L of lipolytic activity was acquired from real experiments. To sum up, the lipolytic activity of wild type strain (1720.4 U/L) increased by 3-fold after UV-induced mutagenesis and medium components optimization (5161.3 U/L).
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http://dx.doi.org/10.1080/10826068.2019.1566148DOI Listing
March 2019

Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents.

Bioorg Chem 2019 03 13;83:559-568. Epub 2018 Nov 13.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran; Departmnt of Pharmaceutical Biomaterials, Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aβ self-aggregation as well as AChE-induced Aβ aggregation. Meanwhile, these compounds could significantly protect PC12 cells against HO-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bioorg.2018.11.010DOI Listing
March 2019

A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels.

Med Hypotheses 2018 Dec 10;121:137-141. Epub 2018 Sep 10.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; School of Pharmacy and Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Thrombosis is a shared perpetrating event in the pathophysiology of several cardiovascular disorders such as ischemic stroke, venous thromboembolism, atherosclerosis, and myocardial infarction. Despite holding a wide range of ammunition in our arsenal to ameliorate such conditions, we are still facing with many stumbling blocks in the satisfactory pharmacotherapy of cardiovascular diseases among which the risk of hemorrhage and life threatening drug interactions can be highlighted. Our hypothesis focuses on mimicking the nature of platelet activation, to design a novel targeted delivery system based on the alterations of a physical parameter, the hemodynamic shear stress, to aim at the offending thrombi in an attempt to offer a noninvasive, rapid, and monitoring-free method that not only can prolong the circulation time of the cargo, but also deliver it locally and reduce both the undesirable adverse effects and drug interactions. Brij52 is our chosen candidate due to its unique non-spherical morphology after forming a niosomal vesicle. We surmised that thanks to its non-spherical shape, diverse shear rates may generate different shear stresses to its equators and axes which might result in the breakdown or at least distortion of niosomal structure under elevated shear stress. The vesicles have to be synthesized in the size of platelets or in the nano-sized scale. In order to prolong the time vesicles are circulating in the blood, PEGylation may help and to make such carriers highly selective to be only activated during pathophysiological clot formation, attachment of domain A1 von Willebrand factor can be of benefit to lead this proposed delivery system to the site of thrombus formation where shear rate exceeds those of 1000 s. There is now an emerging fast growing universal research on shear activated carriers, and the present theory is an endeavor to reach a successful treatment strategy to combat cardiovascular diseases based on the hypothesis that a non-spherical nano-carrier such as Brij 52 niosomal vesicle can be of paramount benefit to deliver current antithrombotic agents in a targeted and controlled manner in the presence of elevated shear stress of the obstructed blood vessels. With more radical advanced drug delivery systems being developed and new strategies being pursued, there will be more options in our arsenal to represent a promising avenue for achieving preventive, well-tolerated, and intelligent drug carriers to circumvent the drawbacks of antithrombotic pharmacotherapy.
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http://dx.doi.org/10.1016/j.mehy.2018.09.022DOI Listing
December 2018

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line.

IET Nanobiotechnol 2018 08;12(5):653-657

Sudent Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.
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http://dx.doi.org/10.1049/iet-nbt.2017.0295DOI Listing
August 2018

Antimicrobial and Antioxidant Activity of the Biologically Synthesized Tellurium Nanorods; A Preliminary Study.

Iran J Biotechnol 2017 29;15(4):268-276. Epub 2017 Dec 29.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Recent theranostic (therapeutic or diagnostic) applications of tellurium nanoparticles have attracted a great interest for development of different methods for synthesis of this valuable nanostructure, especially via biological resources. In the present study, the antimicrobial and antioxidant effects of the tellurium nanorods (Te NRs) biosynthesized by a bacterial strain strain Te were evaluated. The antimicrobial effect of Te NRs and potassium tellurite against different bacterial and fungal pathogens was assessed by microdilution method. Furthermore, the disk diffusion method was used to evaluate the antibacterial effect of the biogenic Te NRs and potassium tellurite against , alone or in combination with various antibiotics. Also, the biogenic Te NRs were investigated for antioxidant activity using 2, 2-diphenyl- 1-picrylhydrazyl (DPPH) scavenging activity and reducing power assay. Transmission electron micrograph (TEM) of the purified Te NRs showed individual and rod-shaped nanostructure (~22 nm diameter by 185 nm in length). Based on the data obtained from both microdilution and disk diffusion method the K TeO exhibited a higher antibacterial and antifungal activity compared to the Te NRs. The measured IC for the biogenic Te NRs (i.e. DPPH radical scavenging activity) was found to be 24.9 μg.mL, while, K TeO has represented only 17.6 ± 0.8 % DPPH radical scavenging effect at the concentration of 160 μg.mL. The reducing power assay revealed a higher electron-donating activity for Te NRs compared to KTeO. Based on the data obtained from both microdilution and disk diffusion method the KTeO exhibited a higher antimicrobial and antifungal activity than Te NRs. Te NRs didn't show the antibacterial effect against the tested bacterial strain: MRSA and showed an inhibitory effect and antibacterial activity of the effective antibiotics. However, more studies should be performed to explore the action mechanism of the produced biogenic Te NRs.
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http://dx.doi.org/10.15171/ijb.1580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903914PMC
December 2017

Novel 3-phenylcoumarin-lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease.

Bioorg Chem 2018 09 2;79:223-234. Epub 2018 May 2.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against HO-induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations. Based on the obtained results, the benzocoumarin derivative 4j with IC value of 7.3 µM was the most potent AChE inhibitor and displayed good inhibition toward intracellular reactive oxygen species (ROS). This compound with antioxidant and metal chelating ability showed also protective effect on cell injury induced by Aβ in SH-SY5Y cells. Although the 8-methoxycoumarin analog 4i was slightly less active than 4j against AChE, but displayed higher protection ability against HO-induced cell death in PC12 and could significantly block Aβ-aggregation. The results suggested that the prototype compounds 4i and 4j might be promising multi-functional agents for the further development of the disease-modifying treatments of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bioorg.2018.04.030DOI Listing
September 2018