Publications by authors named "Mina Saeedi"

56 Publications

Naturally occurring and synthetic peptides: Efficient tyrosinase inhibitors.

J Pept Sci 2021 Apr 15:e3329. Epub 2021 Apr 15.

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

Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment, which is the most important photo protective agent against skin photo carcinogenesis. Excess production of melanin causes hyperpigmentation leading to undesired browning in human skin, fruits, and vegetable as well as plant-derived foods. Moreover, the role of tyrosinase in the onset and progression of various diseases such as cancers, Alzheimer's, and Parkinson diseases has been well documented in the literature. In this respect, tyrosinase inhibitors have been in the center of attention particularly as the efficient skin whitening agents. Among a wide range of compounds possessing anti-tyrosinase activity, peptides both natural and synthetic derivatives have attracted attention due to high potency and safety.
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http://dx.doi.org/10.1002/psc.3329DOI Listing
April 2021

Anti-cholinesterase and Neuroprotective Activities of Sweet and Bitter Apricot Kernels ( L.).

Iran J Pharm Res 2020 ;19(4):216-224

Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Apricot ( L.) is a fruit cultivated in various parts of the world. Both sweet and bitter kernels of apricot have been used for the treatment of different diseases such as loss of memory in Iranian traditional medicine (ITM). In the present study, the inhibitory activity of sweet and bitter extracts of apricot kernels towards cholinesterase (ChE) enzymes, both acetyl and butyrylcholinesterase was examined through Ellman's method. In addition, neuroprotectivity of aqueous extracts and amygdalin were investigated against HO-induced cell death in PC12 neurons. Among them, the best acetylcholinesterase (AChE) inhibitory activity (IC = 134.93 ± 2.88 µg/mL) and neuroprotectivity (-value < 0.0001) were obtained by the aqueous extract of bitter type. It was found that all extracts showed no butyrylcholinesterase (BChE) inhibitory activity.
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http://dx.doi.org/10.22037/ijpr.2019.15514.13139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019877PMC
January 2020

Synthesis, in vitro evaluation, and molecular docking studies of novel hydrazineylideneindolinone linked to phenoxymethyl-1,2,3-triazole derivatives as potential α-glucosidase inhibitors.

Bioorg Chem 2021 Mar 29;111:104869. Epub 2021 Mar 29.

Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

In this work, a novel series of hydrazineylideneindolinone linked to phenoxymethyl-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anti-α-glucosidase activity due to an urgent need to develop effective anti-diabetic agents. Among tested 15 compounds, 8 derivatives (9a, 9b, 9c, 9d, 9e, 9f, 9h, and 9o) demonstrated superior potency compared to that of positive control, acarbose. Particularly, compound 9d possessed the best anti-α-glucosidase activity with around a 46-fold improvement in the inhibitory activity. Additionally, 9d showed a competitive type of inhibition in the kinetic study and the molecular docking study demonstrated that it well occupied the binding pocket of the catalytic center through desired interactions with residues, correlating to the experimental results.
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http://dx.doi.org/10.1016/j.bioorg.2021.104869DOI Listing
March 2021

Recent advances in biological activities of rhodium complexes: Their applications in drug discovery research.

Eur J Med Chem 2021 Apr 23;216:113308. Epub 2021 Feb 23.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Unique structure, characteristic reactivity, and facile synthesis of metal complexes have made them efficient ligands in drug development research. Among them, rhodium complexes have a limited history and there are a few discussions about their biological activities documented in the literature. However, investigation of kinetically inert rhodium complexes has recently attracted lots of attention and especially there are various evidences on their anti-cancer activity. It seems that they can be investigated as a versatile surrogates or candidates for the existing drugs which do not affect selectively or suffer from various side effects. In recent years, there has been an increasing interest in the use of mononuclear rhodium (III) organometallo drugs due to its versatile structurally important aspects to inhibit various enzymes. It has been demonstrated that organometallic Rh complexes profiting from both organic and inorganic aspects have shown more potent biological activities than classical inorganic compartments. In this respect, smart design, use of the appropriate organic ligands, and efficient and user-friendly synthesis of organometallic Rh complexes have played crucial roles in the inducing desirable biological activities. In this review, we focused on the recent advances published on the bioactivity of Rh (III/II/I) complexes especially inhibitory activity, from 2013 till now. Accordingly, considering the structure-activity relationship (SAR), the effect of oxidation state (+1, +2, and +3) and geometry (dimer or monomer complexes with coordination number of 4 and 6) of Rh complexes as well as various ligands on in vitro and in vivo studies was comprehensively discussed.
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http://dx.doi.org/10.1016/j.ejmech.2021.113308DOI Listing
April 2021

Phytocatalytic and cytotoxic activity of the purified laccase from bled resin of Pistacia atlantica Desf.

Int J Biol Macromol 2021 Apr 3;176:394-403. Epub 2021 Feb 3.

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

This study reports an efficient and fast procedure for the purification of laccase (PaL) obtained from the resin of Pistacia atlantica Desf. It was purified by one-step affinity chromatography and showed the specific activity of 393 U/mg with 81.9-fold purification. The molecular weight of PaL was estimated to be approximately 60 kDa using gel electrophoresis SDS-PAGE. Moreover, it depicted diphenolase activity and high affinity towards 2,6-dimethoxy phenol (K = 10.01 ± 0.5 mM) and syringaldazine (K = 6.57 ± 0.2 mM) comparing with plant-origin polyphenol oxidases reported in the literature. It should be noted that PaL possessed optimal activity at pH 7.5 and 45 °C. It also remained stable under different conditions of pH (6.5-8.0), temperature (25-45 °C), and when it was exposed to several metal ions. The MTT and flow cytometry assays demonstrated that the enzyme treatment significantly affected growth of HeLa, HepG2, and MDA-MB-231 cells with LC values of 4.83 ± 0.02, 61 ± 0.31, and 26.83 ± 0.11 μM after 72 h, respectively. NOVELTY STATEMENT: This is the first attempt to isolate and characterize a new oxidoreductase from the resin of Pistacia atlantica Desf., native species of Iran, to recruit it in cytotoxicity researches. In the purification process by an efficient affinity column (SBA-NH-GA), the enzyme was eluted promptly with a satisfied yield. The purified laccase exerted higher affinity to diphenolic compounds and pH-thermal stability compared to other plant-derived polyphenol oxidases. The purified enzyme was found to show anti-oxidant capacity and significantly inhibited the growth of cancerous cells in vitro. PaL showed more cytotoxic activity towards HeLa and MDA-MB-231 cells by induction of apoptosis. The cytotoxic activity of the laccase was measured by flow cytometry.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.212DOI Listing
April 2021

Phytochemical constituents and biological activities of Salvia macrosiphon Boiss.

BMC Chem 2021 Jan 19;15(1). Epub 2021 Jan 19.

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

Salvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and β-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.
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http://dx.doi.org/10.1186/s13065-020-00728-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814726PMC
January 2021

Novel N-benzylpiperidine derivatives of 5-arylisoxazole-3-carboxamides as anti-Alzheimer's agents.

Arch Pharm (Weinheim) 2021 Mar 23;354(3):e2000258. Epub 2020 Nov 23.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The complex pathophysiology of Alzheimer's disease (AD) has prompted researchers to develop multitarget-directed molecules to find an effective therapy against the disease. In this context, a novel series of N-(1-benzylpiperidin-4-yl)-5-arylisoxazole-3-carboxamide derivatives were designed, synthesized, and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro biological evaluation demonstrated that compound 4e was the best AChE (IC  = 16.07 μM) and BuChE inhibitor (IC  = 15.16 μM). A kinetic study of 4e was also conducted, which presented a mixed-type inhibition for both enzymes. Molecular docking studies revealed that compound 4e fitted well into the active sites of AChE and BuChE, forming stable and strong interactions with key residues Glu199, Trp84, Asp72, Tyr121, and Phe288 in AChE and His438, Trp82, Ala328, Tyr332, Phe329, Thr120, and Pro285 in BuChE. Besides, the inhibition of BACE1 by 4e and the biometal chelation activity of 4e were measured. The neuroprotective assessment revealed that 4e exhibited 23.2% protection at 50 µM toward amyloid-beta-induced PC12 neuronal cells. Overall, this study exhibited that compound 4e was a promising compound targeting multiple factors associated with AD.
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http://dx.doi.org/10.1002/ardp.202000258DOI Listing
March 2021

Plant Polyphenols: Natural and Potent UV-Protective Agents for the Prevention and Treatment of Skin Disorders.

Mini Rev Med Chem 2021 ;21(5):576-585

Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Nowadays, destructive and immunosuppressive effects from long-term exposure to UV radiation have been fully investigated and documented in the literature. UV radiation is known as the main cause of skin aging and carcinogenesis. Hence, skin protection against anti-oxidative and immunosuppressive processes is highly in demand. Now, plant polyphenols have been found as a versatile and natural tool for the prevention and treatment of various skin diseases. The presence of a large number of hydroxyl groups in the cyclic structure of polyphenols has induced valuable biological activities. Among them, their UV protective activity has attracted lots of attention due to promising efficacy and simple instruction to use.
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http://dx.doi.org/10.2174/1389557520666201109121246DOI Listing
January 2021

Design and synthesis of multi-target directed 1,2,3-triazole-dimethylaminoacryloyl-chromenone derivatives with potential use in Alzheimer's disease.

BMC Chem 2020 Dec 27;14(1):64. Epub 2020 Oct 27.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Aβ aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC value of 21.71 μM for compound as the most potent compound. Besides, compound could inhibit self-induced Aβ aggregation and AChE-induced Aβ aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver-Burk plot and molecular modeling study showed that compound targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments.
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http://dx.doi.org/10.1186/s13065-020-00715-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592376PMC
December 2020

Synthesis of 4-alkylaminoimidazo[1,2-a]pyridines linked to carbamate moiety as potent α-glucosidase inhibitors.

Mol Divers 2020 Oct 12. Epub 2020 Oct 12.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

In this work, various imidazo[1,2-a]pyridines linked to carbamate moiety were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity. Among synthesized compounds, 4-(3-(tert-Butylamino)imidazo[1,2-a]pyridin-2-yl)phenyl p-tolylcarbamate (6d) was the most potent compound (IC = 75.6 µM) compared with acarbose as the reference drug (IC = 750.0 µM). Kinetic study of compound 6d indicated a competitive inhibition. Also, the molecular docking study suggested desired interactions with the active site residues. In particular, hydrogen bonds and electrostatic interactions constructed by compound 6d afforded well-oriented conformation in the 3A4A active site.
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http://dx.doi.org/10.1007/s11030-020-10137-8DOI Listing
October 2020

N-Cyclohexylimidazo[1,2-a]pyridine derivatives as multi-target-directed ligands for treatment of Alzheimer's disease.

Bioorg Chem 2020 10 28;103:104146. Epub 2020 Jul 28.

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

Alzheimer's disease (AD) is the most common form of dementia. While drugs that target several pathways underlying AD have been proposed, effective treatments remain to be discovered. BACE1, an enzyme associated with AD progression, is a promising target for developing anti-Alzheimer drugs. To find novel multifunctional anti-Alzheimer agents, we designed and synthesized a series of new substituted benzyl-1H-1,2,3-triazol-4-yl-N-cyclohexylimidazo[1,2-a]pyridin-3-amine. The in vitro screening results revealed that most of the compounds exhibited moderate to potent BACE1 and BuChE inhibitory and antioxidant activities. Compounds 7f and 7g, bearing dichloro (2,3-Cl and 3,4-Cl) moieties on the benzyl pendant were selected as the most active compounds in our BACE1 inhibitory assay with respective IC values of about 12 and 8.9 μM. In addition, compounds 7g and 7h (4-bromo derivative) showed the highest BuChE inhibitory activity with IC of 3.2 and 2.5 µM, respectively. Compound 7g also possessed antioxidant activity with an IC value of 10.2 μM and metal chelation potential. Moreover, docking studies were performed to investigate the possible mechanism of inhibition. Taken together, we demonstrate that N-cyclohexylimidazo[1,2-a]pyridine containing triazole motif derivatives deserve further investigation for anti-Alzheimer drug development.
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http://dx.doi.org/10.1016/j.bioorg.2020.104146DOI Listing
October 2020

Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease.

Arch Pharm (Weinheim) 2020 Oct 13;353(10):e2000101. Epub 2020 Jul 13.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (βA) aggregation and β-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.
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http://dx.doi.org/10.1002/ardp.202000101DOI Listing
October 2020

Phytochemical investigation and anticholinesterase activity of ethyl acetate fraction of Houtt. seeds.

Nat Prod Res 2020 Jul 8:1-7. Epub 2020 Jul 8.

Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran.

In this work, -hexane, chloroform, and ethyl acetate fractions of the methanol extract of Houtt. seeds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) Ellman's method. It was found that all fractions depicted no anti-AChE activity, however, they were active toward BChE with IC values of 361.8, 215.0, and 145.8 µg/mL, respectively comparing with donepezil as the reference drug (IC = 1.97 µg/mL). The ethyl acetate fraction which also showed high neuroprotectivity and metal chelating ability was selected for the phytochemical analysis. Our results confirmed the presence of trimyristin and 5,7-diacetyl chrysin (reported for the first time in ) in the corresponding fraction.
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http://dx.doi.org/10.1080/14786419.2020.1788555DOI Listing
July 2020

Design and Synthesis of Novel Arylisoxazole-Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease.

Chem Biodivers 2020 May 15;17(5):e1900746. Epub 2020 Apr 15.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, 14155, Tehran, Iran.

A novel series of hybrid arylisoxazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5-(3-nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide depicted the most acetylcholinesterase (AChE) inhibitory activity (IC =1.23 μm) and 5-(3-chlorophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC =9.71 μm). 5-(3-Nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide was further investigated for its BACE1 inhibitory activity as well as neuroprotectivity and metal chelating ability as important factors involved in onset and progress of Alzheimer's disease. It could inhibit BACE1 by 48.46 % at 50 μm. It also showed 6.4 % protection at 25 μm and satisfactory chelating ability toward Zn , Fe , and Cu ions. Docking studies of 5-(3-nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide and 5-(3-chlorophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.
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http://dx.doi.org/10.1002/cbdv.201900746DOI Listing
May 2020

Investigation of and gene alternations in strains exposed to kombucha fermented tea.

Curr Med Mycol 2019 Sep;5(3):36-42

Division of Molecular Biology, Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background And Purpose: is one of the most common opportunistic fungus, which causes infection in immunocompromised and neutropenic patients. The current guidelines recommend voriconazole as the initial therapeutic and prophylactic agent for almost all cases, especially in patients with organ transplants, which leads to increased medication resistance in . The aim of the present study was to evaluate the antifungal activity and effect of kombucha as a natural compound on growth, as well as on the expression of and genes.

Materials And Methods: A panel of 15 strains with two quality controls of CM237 and CM2627 as susceptible and resistant strains were obtained from Tehran Medical Mycology Laboratory, Tehran,Iran(TMML).Antifungal susceptibility testing assay was performed according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. Moreover, the mycelial dry weight of the fungus was calculated before and after being treated with kombucha. In addition, the quantitative changes in the expression of and genes were analyzed by real-time polymerase chain reaction (real-time PCR) technique.

Results: In the present study, the minimum inhibitory concentration ranges of kombucha were measured at 6,170 and 12,300 μg/mL for ten azole-susceptible strains and 24,700 μg/mL for five resistant strains. Moreover, changes in mycelial dry weight under kombucha treatment conditions underwent a significant reduction (). A coordinate down-regulation of expression in and genes was observed in all azole-susceptible and -resistant strains, after treating the fungus with different concentrations of kombucha ().

Conclusion: According to the obtained results, kombucha as a natural antioxidant , can exert inhibitory effects against the growth and expression of some genes in strains.
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http://dx.doi.org/10.18502/cmm.5.3.1745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910712PMC
September 2019

Design, synthesis, in vitro, and in silico studies of novel diarylimidazole-1,2,3-triazole hybrids as potent α-glucosidase inhibitors.

Bioorg Med Chem 2019 12 15;27(23):115148. Epub 2019 Oct 15.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

In this work, new derivatives of diarylimidazole-1,2,3-triazole 7a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity. All compounds showed potent inhibitory activity in the range of IC = 90.4-246.7 µM comparing with acarbose as the standard drug (IC = 750.0 µM). Among the synthesized compounds, compounds 7b, 7c, and 7e were approximately 8 times more potent than acarbose. The kinetic study of those compounds indicated that they acted as the competitive inhibitors of α-glucosidase. Molecular docking studies were also carried out for compounds 7b, 7c, and 7e using modeled α-glucosidase to find the interaction modes responsible for the desired inhibitory activity.
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http://dx.doi.org/10.1016/j.bmc.2019.115148DOI Listing
December 2019

Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study.

Bioorg Chem 2019 11 10;92:103192. Epub 2019 Aug 10.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC = 5.96 µM) and compound 5j also from the same series of compounds containing phenyl group connected to isoxazole ring demonstrated the most promising inhibitory activity against BChE (IC = 0.32 µM). Also, kinetic study demonstrated competitive inhibition mode for both AChE and BChE inhibitory activity. Docking study was also performed for those compounds and desired interactions with those active site amino acid residues were confirmed through hydrogen bonding as well as π-π and π-anion interactions. In addition, the most potent compounds were tested against BACE1 and their neuroprotectivity on Aβ-treated neurotoxicity in PC12 cells which depicted negligible activity. It should be noted that most of the synthesized compounds from both categories 5a-i and 5j-q showed a significant selectivity toward BChE. However, series 5j-q were more active toward AChE than series 5a-i.
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http://dx.doi.org/10.1016/j.bioorg.2019.103192DOI Listing
November 2019

Synthesis of highly functionalized organic compounds through Ugi post-transformations started from propiolic acids.

Mol Divers 2020 Aug 19;24(3):855-887. Epub 2019 Jul 19.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

The Ugi four-component (Ugi-4CR) post-transformation reactions have emerged as a prominent tool to construct complex organic molecules utilizing readily available starting materials. Propiolic acid derivatives are promising choice of substrates due to their versatile reactivity. Over the last decade, Ugi post-transformations starting from propiolic acid derivatives have experienced a rapid growth to afford atom-efficient processes and enantioselective transformations. This review has focused on the recent advances in the Ugi post-transformations starting from propiolic acids and their application for the preparation of highly functionalized organic compounds.
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http://dx.doi.org/10.1007/s11030-019-09975-yDOI Listing
August 2020

Design, synthesis, in vivo, and in silico evaluation of new coumarin-1,2,4-oxadiazole hybrids as anticonvulsant agents.

Bioorg Chem 2019 08 18;89:102989. Epub 2019 May 18.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of coumarin-1,2,4-oxadiazole hybrids were designed, synthesized, and evaluated as anticonvulsant agents. The title compounds were easily synthesized from reaction of appropriate coumarins and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazole derivatives. In vivo anticonvulsant activity of the synthesized compounds were determined using pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures confirming that they were more effective against MES test than PTZ test. It should be noted that compounds 3b, 3c, and 3e showed the best activity in MES model which possessed drug-like properties with no neurotoxicity. Anticonvulsant activity of the most potent compound 3b was remarkably reduced after treatment with flumazenil which confirmed the participation of a benzodiazepine mechanism in the anticonvulsant activity. Also, docking study of compound 3b in the BZD-binding site of GABA receptor confirmed possible binding of 3b to the BZD receptors.
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http://dx.doi.org/10.1016/j.bioorg.2019.102989DOI Listing
August 2019

Serum and salivary interleukin-4 levels in patients with oral lichen planus: A systematic review and meta-analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Aug 16;128(2):123-131. Epub 2019 Apr 16.

Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objective: Cytokines have an important role in keratinocyte immune damage and can act in the pathogenesis of different cutaneous diseases. Accordingly, in the literature, interleukin 4 (IL-4) concentration has been previously investigated in patients affected by oral lichen planus (OLP).

Study Design: The present meta-analysis evaluated the serum and salivary levels of IL-4 in connection with several OLP variants. The search was performed from 1995 in Cochrane Library and 1983 in Scopus, PubMed, and Web of Science to September 2018. The quality of the studies included in the meta-analysis was assessed using the Newcastle-Ottawa Scale assessment. The analyses were done by Review Manager 5.3 using mean difference (MD) and 95% confidence intervals (CIs).

Results: Out of 108 studies retrieved in the databases, only 10 were included and analyzed in quantitative synthesis. The pooled MD of the serum and salivary IL-4 levels in OLP patients compared with the controls was 6.36 picograms/milliliter (pg/mL) (95% CI: 1.47, 11.24; P = .01) and 2.67 pg/mL (95% CI: 2.66, 2.68; P < .00001), respectively. In addition, the pooled MD of serum and salivary IL-4 level was 1.30 pg/mL (95% CI: -0.35, 2.95; P = .12) and 1.83 pg/mL (95% CI: 0.26, 3.40; P = .02), respectively, in patients with erosive, erythematous, bullous, and ulcerative variants of OLP compared with patients with reticular OLP.

Conclusions: This meta-analysis found that OLP patients present elevated serum and salivary IL-4 levels, thus indicating that IL-4 may represent a potential salivary biomarker for the disease. By contrast, clinicians must be aware that even other factors (e.g., secondary infection) may influence its concentration.
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http://dx.doi.org/10.1016/j.oooo.2019.04.003DOI Listing
August 2019

Design and Synthesis of Novel Cytotoxic Indole-Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study.

Chem Biodivers 2019 Apr 3;16(4):e1800470. Epub 2019 Apr 3.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, 1417653761, Tehran, Iran.

In this work, two novel series of indole-thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF-7, A-549, and Hep-G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A-549 and Hep-G2 than MCF-7. Among them, (2E)-2-{[2-(4-chlorophenyl)-1H-indol-3-yl]methylidene}-N-(4-methoxyphenyl)hydrazinecarbothioamide (8l) was found to be the most potent compound against A-549 and Hep-G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A-549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.
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http://dx.doi.org/10.1002/cbdv.201800470DOI Listing
April 2019

Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti-Alzheimer's Agents.

Chem Biodivers 2019 Apr 3;16(4):e1800488. Epub 2019 Apr 3.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, 1416753955, Iran.

Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal-chelating properties. Among the synthesized compounds, 14-amino-13-(3-nitrophenyl)-2,3,4,13-tetrahydro-1H-benzo[6,7]chromeno[2,3-b]quinoline-7,12-dione (6m) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC s of 0.86 and 6.03 μm, respectively. Also, the compound could inhibit β-secretase 1 (BACE1) with IC =19.60 μm and showed metal chelating ability toward Cu , Fe , and Zn . In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.
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http://dx.doi.org/10.1002/cbdv.201800488DOI Listing
April 2019

Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole-Phenylpiperazine Derivatives.

Chem Biodivers 2019 Feb 30;16(2):e1800433. Epub 2019 Jan 30.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, 14155 Tehran, Iran.

In this work, a novel series of arylisoxazole-phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5-(2-chlorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5c) was the most potent AChE inhibitor with IC of 21.85 μm. It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5-(2-fluorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5a) was the most active anti-BChE derivative (IC =51.66 μm). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC =76.78 μm. Finally, neuroprotectivity of compound 5c on Aβ-treated neurotoxicity in PC12 cells depicted low activity.
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http://dx.doi.org/10.1002/cbdv.201800433DOI Listing
February 2019

Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives.

Bioorg Chem 2019 03 30;83:391-401. Epub 2018 Oct 30.

Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC = 1.80 µM), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC = 21.13 µM confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against HO-induced cell death in PC12 neurons at 50 µM as well as metal chelating ability toward Fe, Cu, and Zn ions.
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http://dx.doi.org/10.1016/j.bioorg.2018.10.065DOI Listing
March 2019

Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer's compounds: In vitro and in vivo biological evaluation and docking study.

Bioorg Chem 2019 03 28;83:303-316. Epub 2018 Oct 28.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A new series of tacrine-coumarin hybrids linked to 1,2,3-triazole were designed, synthesized, and tested as potent dual binding site cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer's disease (AD). Among them, compound 8e was the most potent anti-AChE derivative (IC = 27 nM) and compound 8m displayed the best anti-BChE activity (IC = 6 nM) much more active than tacrine and donepezil as the reference drugs. Compound 8e was also evaluated for its BACE1 inhibitory activity and neuroprotectivity against PC12 cells exposed to Aβ which indicated low activity. Finally, in vivo studies by Morris water maze task showed that compound 8e significantly reversed scopolamine-induced memory deficit in rats.
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http://dx.doi.org/10.1016/j.bioorg.2018.10.056DOI Listing
March 2019

Design and synthesis of novel quinazolinone-1,2,3-triazole hybrids as new anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and docking study.

Bioorg Chem 2019 03 11;83:161-169. Epub 2018 Oct 11.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC values in the range of 181.0-474.5 µM) even much more potent than standard drug acarbose (IC = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with K value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.
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http://dx.doi.org/10.1016/j.bioorg.2018.10.023DOI Listing
March 2019

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents.

Anticancer Agents Med Chem 2019 ;19(2):265-275

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives.

Objective: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated.

Methods: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death.

Results: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods.

Conclusion: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.
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http://dx.doi.org/10.2174/1871520618666180903100835DOI Listing
November 2019

Synthesis of New Benzimidazole-1,2,3-triazole Hybrids as Tyrosinase Inhibitors.

Chem Biodivers 2018 Jul 21;15(7):e1800120. Epub 2018 Jun 21.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, P.O. Box 14155, 6451, Tehran, Iran.

A novel series of benzimidazole-1,2,3-triazole hybrids containing substituted benzyl moieties were designed, synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 2-(4-{[1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6g) and 2-(4-{[1-(4-bromobenzyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1H-benzimidazole (6h) exhibited effective inhibitory activity with IC values of 9.42 and 10.34 μm, respectively, comparable to that of kojic acid as the reference drug (IC = 9.28 μm). Kinetic study of compound 6g confirmed mixed-type inhibitory activity towards tyrosinase indicating that it can bind to free enzyme as well as enzyme-substrate complex. Also, molecular docking analysis was performed to determine the binding mode of the most potent compounds (6g and 6h) in the active site of tyrosinase. Consequently, 6g and 6h derivatives might serve as promising candidates in cosmetics, medicine or food industry, and development of such compounds may be of an interest.
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http://dx.doi.org/10.1002/cbdv.201800120DOI Listing
July 2018

Novel quinazolin-4(3H)-one linked to 1,2,3-triazoles: Synthesis and anticancer activity.

Chem Biol Drug Des 2018 07 18;92(1):1373-1381. Epub 2018 May 18.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

In this work, a wide range of novel quinazolin-4(3H)-one linked to 1,2,3-triazoles was designed, synthesized, and evaluated against a panel of three human breast (MDA-MB-231, MCF-7, T-47D), lung (A549), and prostate (PC3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3-triazole moieties. According to the calculated IC values, compounds 6q, 6w, and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non-small-cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g, 6u, 6w, and 6x over the EGFR active site. The most promising compounds, 6q and 6u, possessing 3-methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction.
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http://dx.doi.org/10.1111/cbdd.13203DOI Listing
July 2018

Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends Towards Future Drugs.

Curr Med Chem 2019 ;26(13):2389-2406

Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, United States.

Background: Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility.

Methods: Different medical research engines such as, GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer-reviewed journals were considered.

Results: Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer.

Conclusion: The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detailed studies are needed to understand the full potential of glycosides for clinical utility.
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http://dx.doi.org/10.2174/0929867325666180403145137DOI Listing
July 2019