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+/-0.62muM) and BChE (IC50; 147.75+/-0.67muM) enzymes. Eserine (IC50; 0.04+/-0.01muM) 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 25muM and with 2.41% cell viability at 50muMamong library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics.
        
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Arfan M, Siddiqui SZ, Abbasi MA, Rehman A, Shah SAA, Ashraf M, Rehman J, Saleem RSZ, Khalid H, Hussain R, Khan U (2018) 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 Pak J Pharm Sci31: 2697-2708
Arfan M, Siddiqui SZ, Abbasi MA, Rehman A, Shah SAA, Ashraf M, Rehman J, Saleem RSZ, Khalid H, Hussain R, Khan U (2018) Pak J Pharm Sci31: 2697-2708