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

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

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 presenc...

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Main Authors: Siddiqui, Sabahat Zahra, Abbasi, Muhammad Athar, Rehman, Aziz-ur, Irshad, Misbah, Shahzad, Babar, Mohd Ashraf, Ahmad, Ahmad, Irshad, Lodhi, Muhammad A., Mirza, Bushra, Ismail, Hammad, Akhtar, Muhammad Nadeem
Format: Article
Language:English
Published: IndianScience.in 2014
Subjects:
QD Chemistry
Online Access:http://umpir.ump.edu.my/id/eprint/7988/
http://umpir.ump.edu.my/id/eprint/7988/
http://umpir.ump.edu.my/id/eprint/7988/1/fist-2014-nadeem-synthesis_pharmacological.pdf
id ump-7988
recordtype eprints
spelling ump-79882019-07-16T06:40:22Z http://umpir.ump.edu.my/id/eprint/7988/ 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 Abbasi, Muhammad Athar Rehman, Aziz-ur Irshad, Misbah Shahzad, Babar Mohd Ashraf, Ahmad Ahmad, Irshad Lodhi, Muhammad A. Mirza, Bushra Ismail, Hammad Akhtar, Muhammad Nadeem QD Chemistry 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. IndianScience.in 2014 Article PeerReviewed pdf en cc_by http://umpir.ump.edu.my/id/eprint/7988/1/fist-2014-nadeem-synthesis_pharmacological.pdf 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 https://iajpr.com/archive/volume-4/august-2014#
repository_type Digital Repository
institution_category Local University
institution Universiti Malaysia Pahang
building UMP Institutional Repository
collection Online Access
language English
topic QD Chemistry
spellingShingle QD Chemistry
Siddiqui, Sabahat Zahra
Abbasi, Muhammad Athar
Rehman, Aziz-ur
Irshad, Misbah
Shahzad, Babar
Mohd Ashraf, Ahmad
Ahmad, Irshad
Lodhi, Muhammad A.
Mirza, Bushra
Ismail, Hammad
Akhtar, Muhammad Nadeem
Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
description 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.
format Article
author Siddiqui, Sabahat Zahra
Abbasi, Muhammad Athar
Rehman, Aziz-ur
Irshad, Misbah
Shahzad, Babar
Mohd Ashraf, Ahmad
Ahmad, Irshad
Lodhi, Muhammad A.
Mirza, Bushra
Ismail, Hammad
Akhtar, Muhammad Nadeem
author_facet Siddiqui, Sabahat Zahra
Abbasi, Muhammad Athar
Rehman, Aziz-ur
Irshad, Misbah
Shahzad, Babar
Mohd Ashraf, Ahmad
Ahmad, Irshad
Lodhi, Muhammad A.
Mirza, Bushra
Ismail, Hammad
Akhtar, Muhammad Nadeem
author_sort Siddiqui, Sabahat Zahra
title Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
title_short Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
title_full Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
title_fullStr Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
title_full_unstemmed Synthesis Pharmacological Evaluation, Molecular Docking And Cytotoxicty Studies On Some N-Substituted 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2yl-2-Sulfanyl Acetamides
title_sort synthesis pharmacological evaluation, molecular docking and cytotoxicty studies on some n-substituted 5-[(4-chlorophenoxy)methyl]-1,3,4-oxadiazole-2yl-2-sulfanyl acetamides
publisher IndianScience.in
publishDate 2014
url http://umpir.ump.edu.my/id/eprint/7988/
http://umpir.ump.edu.my/id/eprint/7988/
http://umpir.ump.edu.my/id/eprint/7988/1/fist-2014-nadeem-synthesis_pharmacological.pdf
first_indexed 2023-09-18T22:05:12Z
last_indexed 2023-09-18T22:05:12Z
_version_ 1777414661971378176

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