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Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides

Siddiqui, Sabahat Zahra and Abbasi, Muhammad Athar and Rehman, Aziz-ur and Irshad, Misbah and Shahzad, Babar and Mohd Ashraf, Ahmad and Ahmad, Irshad and Lodhi, Muhammad A. and Mirza, Bushra and Ismail, Hammad and Akhtar, Muhammad Nadeem (2014) Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides. Indo American Journal Of Pharmaceutical Research, 4 (8). pp. 3603-3617. ISSN 2231-6876

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Abstract

The framework of our systematic efforts focuses on the synthesis of N-substituted 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2yl-2-sulfanyl acetamides. 4-Chlorophenoxyacetic acid (1) was utilized as a precursor for the synthesis of parent 1,3,4-oxadiazole moiety. Esterification of 1in the presence of catalytic amount of concentrated sulfuric acid and absolute alcohol generated ethyl 2-(4-chlorophenoxy)acetate (2) which was treated with hydrazine hydrate to yield 2-(4-chlorophenoxy)acetohydrazide (3). Ring closure reaction of 3 with carbon disulfide and alcoholic potassium hydroxide afforded [5-(4-chlorophenoxy)methyl)]-1,3,4-oxadiazole-2-thiol (4). Finally, substitution at thiol position of 4 with electrophiles, N-substituted-2-bromoacetamides (6a-p) in polar aprotic solvent and LiH yielded various N-substituted 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2yl-2-sulfanyl acetamides (7a-p). IR, 1H-NMR and EI-MS spectral analysis data unequivocally confirmed all the substitutions on 1,3,4-oxadiazole-2-thiol core. It was recognized that the synthesized derivatives are potential anti-bacterial agents against both gram negative and gram positive bacteria and moderate inhibitors of α-chymotrypsin enzyme. In vitro screening against various bacterial strains unleashed their anti-bacterial potential, especially 5-[(4-chlorophenoxy)methyl]-1,3,4-oxadiazol-2yl-N-(3,4-dimethylphenyl)-2-sulfanyl acetamide (7o) exhibited marvelous activity when compared with standard ciprofloxacin against S.typhi (-), K.pneumonae (-) and S. aureus (+).Compounds were computationally docked with the α-chymotrypsin enzyme protein to unravel the active binding sites which displayed significant correlation with the bioactivity data. It can be envisioned that the amalgamation of 5-[(4-chlorophenoxy)methyl]-1,3,4-oxadiazole-2-thiol with N-substituted-2-bromoacetamides generated N-substituted 5-[(4-chlorophenoxy)methyl]-1,3,4-oxadiazole-2yl-2-sulfanyl acetamides having tremendous antibacterial activity and moderate anti-enzymatic potential. Moreover, substitutions on the oxadiazole moiety lead to the discovery of less cytotoxic compounds as evident from the cytotoxicity data.

Item Type: Article
Uncontrolled Keywords: N-Substituted-5- [(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides; Spectral Analysis; Pharmacological Screening; Molecular Docking
Subjects: Q Science > QD Chemistry
Faculty/Division: Faculty of Industrial Sciences And Technology
Depositing User: Noorul Farina Arifin
Date Deposited: 30 Dec 2014 03:50
Last Modified: 16 Jul 2019 06:40
URI: http://umpir.ump.edu.my/id/eprint/7988
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