Publications by authors named "Nima Sepehri"

8 Publications

  • Page 1 of 1

The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity.

Bioorg Med Chem 2021 Apr 27;36:116044. Epub 2021 Jan 27.

Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC value of 0.46 and 0.50 µM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure-activity relationship analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116044DOI Listing
April 2021

Novel quinazolin-sulfonamid derivatives: synthesis, characterization, biological evaluation, and molecular docking studies.

J Biomol Struct Dyn 2020 Nov 23:1-12. Epub 2020 Nov 23.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin-sulfonamid derivatives () were synthesized, characterized and evaluated for their antidiabetic, anticholinergics, and antiepileptic activity. These synthesized novel quinazolin-sulfonamid derivatives () were found to be effective inhibitor molecules for the α-glycosidase, human carbonic anhydrase I and II (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzyme, with Ki values in the range of 100.62 ± 13.68-327.94 ± 58.21 nM for α-glycosidase, 1.03 ± 0.11-14.87 ± 2.63 nM for hCA I, 1.83 ± 0.24-15.86 ± 2.57 nM for hCA II, 30.12 ± 3.81-102.16 ± 13.87 nM for BChE, and 26.16 ± 3.63-88.52 ± 20.11 nM for AChE, respectively. In the last step, molecular docking calculations were made to compare biological activities of molecules against enzymes which are achethylcholinesterase, butyrylcholinesterase and α-glycosidase. Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1847193DOI Listing
November 2020

Synthesis, characterization, molecular docking, and biological activities of coumarin-1,2,3-triazole-acetamide hybrid derivatives.

Arch Pharm (Weinheim) 2020 Oct 9;353(10):e2000109. Epub 2020 Jul 9.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin-1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin-1,2,3-triazole-acetamide hybrids showed K values in the range of 483.50-1,243.04 nM against hCA I, 508.55-1,284.36 nM against hCA II, 24.85-132.85 nM against AChE, 27.17-1,104.36 nM against BChE, 590.42-1,104.36 nM against α-Gly, and 55.38-128.63 nM against α-Amy. The novel coumarin-1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin-1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.202000109DOI Listing
October 2020

Biotin decorated PLGA nanoparticles containing SN-38 designed for cancer therapy.

Artif Cells Nanomed Biotechnol 2017 May 2;45(3):495-504. Epub 2016 May 2.

a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Islamic Republic of Iran.

Active targeted chemotherapy is expected to provide more specific delivery of cytotoxic drugs to the tumor cells and hence reducing the side effects on healthy tissues. Due to the over expression of biotin receptors on cancerous cells as a result of further requirement for rapid proliferations, biotin can be a good candidate as a targeting agent. In this study, biotin decorated PLGA nanoparticles (NPs) containing SN-38 were prepared and in vitro studies were evaluated for their improved anti-cancer properties. In conclusion, biotin targeted PLGA NPs containing SN-38 showed preferential anticancer properties against tumor cells with biotin receptor over expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2016.1178130DOI Listing
May 2017

Human serum albumin conjugates of 7-ethyl-10-hydroxycamptothecin (SN38) for cancer treatment.

Biomed Res Int 2014 7;2014:963507. Epub 2014 May 7.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran ; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.

SN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan, which has been approved for treatment of metastatic colorectal cancer. Considering the notable potency of SN38, it has been introduced as an anticancer candidate. In this study, human serum albumin (HSA) conjugates of SN38 were formulated to overcome the solubility problem beside improving the active form stability and tumor tissue targeting. In this target, two different molar ratios of conjugates (SN38 : HSA 15 : 1 and 60 : 1) were prepared by derivatization of 20-hydroxyl group of SN38 with glycine, followed by addition of succinyl group to glycine through which HSA was covalently attached. The conjugates with particle size of about 100 nm revealed enhanced water solubility and were relatively stable in neutral and acidic solutions. For SN38-HSA-15 and SN38-HSA-60 IC50 values were compared with irinotecan in HT-29 human colon cancer cells. Furthermore, biodistribution studies of SN38-HSA conjugate resulted in proper blood concentration level within 4 h. Moreover, blood cytotoxicity assay revealed no toxicity effect on liver and spleen. Collectively, our present investigation offers a water-soluble form of SN38 attached to HSA and suggests using favorable properties as a promising anticancer agent for further preclinical and clinical investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/963507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033423PMC
November 2015

SN38 polymeric nanoparticles: in vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan.

Int J Pharm 2014 Aug 29;471(1-2):485-97. Epub 2014 May 29.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

SN38 (7-ethyl-10-hydroxyl camptothecin), a potent metabolite of irinotecan, has been considered as an anticancer candidate. Its clinical development has been hampered due to its poor solubility. As a result, SN38 loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) was developed in current study to solve its poor water solubility problem while maintaining its cytotoxicity against cancer cells. PLGA NPs were prepared using modified emulsification-solvent evaporation technique and their characteristics were optimized by central composite experimental design in which average size, entrapment efficiency and drug loading were 170.5±11.87 nm, 77.35%±2.314 and 5.95%±0.087, respectively. Scanning electron microscopy and in vitro studies consisting of drug release and cytotoxicity in 4T1 breast cancer cells followed by in vivo biodistribution and blood cytotoxicity were carried out. Therapeutic efficacy of SN38-NPs was evaluated in xenograft balb/c animal with 4T1 breast cancer. The results demonstrated that the treatment with SN38-NPs was more efficacious in comparison with irinotecan. In conclusion, superior cytotoxic effect and improved in vivo antitumor efficacy of SN38-NPs versus irinotecan introduced SN38-NPs as a promising candidate for cancer treatment investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2014.05.046DOI Listing
August 2014

Zinc protoporphyrin polymeric nanoparticles: potent heme oxygenase inhibitor for cancer therapy.

Pharm Res 2014 Aug 21;31(8):2124-39. Epub 2014 Feb 21.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor.

Methods: PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis.

Results: NPs average size, entrapment efficiency and drug loading were 100.12 ± 5.345 nm, 55.6% ± 2.49 and 7.98% ± 0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC50 value of ZnPP-NPs for PC3 human prostate cancer cells was found to be 2.14 ± 0.083 μM.

Conclusion: In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-014-1313-7DOI Listing
August 2014

Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.

J Pharm Sci 2009 Aug;98(8):2718-30

Novel Drug Delivery Systems Laboratory, Faculty of Pharmacy, Department of Pharmaceutics, Tehran University of Medical Sciences, PO Box 14155-6451, Tehran, Iran.

Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer. A high-performance liquid chromatography method was developed for the determination of DTX-albumin conjugate. T47D and SKOV3 cells were used for the evaluation of the in vitro cytotoxicity of the conjugate by MTT assay. Studies were then done on balb/c mice to elucidate the tissue distribution of conjugates after intravenous administration. The albumin-conjugated formulation of DTX with the particle size of 90-110 nm showed enhanced solubility and in vivo characteristics and significantly higher cytotoxicity against tumor cells, for example, IC50 of 6.30 +/- 0.73 nM for T47D cell line compared to free DTX with IC50 of 39.4 +/- 1.75 nM. Conjugation also maintained DTX plasma level at 16.19% up to 2 h after injection compared with 2.51% for Taxotere, hence increasing the chance of nanoparticles uptake by tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jps.21599DOI Listing
August 2009