Cargando…

Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides

BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against...

Descripción completa

Detalles Bibliográficos
Autores principales: Yadav, Snehlata, Lim, Siong Meng, Ramasamy, Kalavathy, Vasudevan, Mani, Shah, Syed Adnan Ali, Mathur, Abhishek, Narasimhan, Balasubramanian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971037/
https://www.ncbi.nlm.nih.gov/pubmed/29804151
http://dx.doi.org/10.1186/s13065-018-0432-3
_version_ 1783326223503458304
author Yadav, Snehlata
Lim, Siong Meng
Ramasamy, Kalavathy
Vasudevan, Mani
Shah, Syed Adnan Ali
Mathur, Abhishek
Narasimhan, Balasubramanian
author_facet Yadav, Snehlata
Lim, Siong Meng
Ramasamy, Kalavathy
Vasudevan, Mani
Shah, Syed Adnan Ali
Mathur, Abhishek
Narasimhan, Balasubramanian
author_sort Yadav, Snehlata
collection PubMed
description BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase. RESULTS: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC(50) = 0.0047 µM/ml) and compound 10 (IC(50) = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate. CONCLUSIONS: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.
format Online
Article
Text
id pubmed-5971037
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-59710372018-06-14 Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides Yadav, Snehlata Lim, Siong Meng Ramasamy, Kalavathy Vasudevan, Mani Shah, Syed Adnan Ali Mathur, Abhishek Narasimhan, Balasubramanian Chem Cent J Research Article BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase. RESULTS: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC(50) = 0.0047 µM/ml) and compound 10 (IC(50) = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate. CONCLUSIONS: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents. Springer International Publishing 2018-05-26 /pmc/articles/PMC5971037/ /pubmed/29804151 http://dx.doi.org/10.1186/s13065-018-0432-3 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yadav, Snehlata
Lim, Siong Meng
Ramasamy, Kalavathy
Vasudevan, Mani
Shah, Syed Adnan Ali
Mathur, Abhishek
Narasimhan, Balasubramanian
Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title_full Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title_fullStr Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title_full_unstemmed Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title_short Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides
title_sort synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1h-benzo[d]imidazol-2-ylthio)-n-substituted acetamides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971037/
https://www.ncbi.nlm.nih.gov/pubmed/29804151
http://dx.doi.org/10.1186/s13065-018-0432-3
work_keys_str_mv AT yadavsnehlata synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT limsiongmeng synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT ramasamykalavathy synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT vasudevanmani synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT shahsyedadnanali synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT mathurabhishek synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides
AT narasimhanbalasubramanian synthesisandevaluationofantimicrobialantitubercularandanticanceractivitiesof21benzoyl1hbenzodimidazol2ylthionsubstitutedacetamides