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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

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

Pak J Pharm Sci. 2018 Nov;31(6 (Supplementary):2697-2708.

PMID: 30587482

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP100094-A 4-Methoxybenzoic acid 4-Methoxybenzoic acid 100-09-4 Price
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