Biomaterial Database

Synthesis, in vitro and in silico studies of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols as cholinesterase inhibitors. 2018

Muhammad Arfan, and Sabahat Zahra Siddiqui, and Muhammad Athar Abbasi, and Azizur Rehman, and Syed Adnan Ali Shah, and Muhammad Ashraf, and Jameel Rehman, and Rahman Shah Zaib Saleem, and Hira Khalid, and Rashid Hussain, and Uzman Khan

Department of Chemistry, Government College University, Lahore, Pakistan.

The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide (1) was cyclized with phenyl isothiocyanate (2) via 2-(4-methoxybenzoyl)-N-phenylhydrazinecarbothioamide (3); an intermediate to 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-thiol (4). The electrophiles; alkyl halides 5(a-g) were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols 6(a-g). Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-(n-heptylthio)-5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole; 6g against AChE (IC50; 38.35±0.62μM) and BChE (IC50; 147.75±0.67μM) enzymes. Eserine (IC50; 0.04±0.01μM) was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability (6g) at 25μM and with 2.41% cell viability at 50μMamong library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics.

UI	MeSH Term	Description	Entries
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013438	Sulfhydryl Compounds	Compounds containing the -SH radical.	Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D014230	Triazoles	Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.	Triazole
D045325	HCT116 Cells	Human COLORECTAL CARCINOMA cell line.	HCT 116 Cells,HCT-116 Cells,Cell, HCT 116,Cell, HCT-116,Cell, HCT116,Cells, HCT 116,Cells, HCT-116,Cells, HCT116,HCT 116 Cell,HCT-116 Cell,HCT116 Cell
D062105	Molecular Docking Simulation	A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.	Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking