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Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis

Mycobacterium tuberculosis resistance to commercially available drugs is increasing day by day. To address this issue, various strategies were planned and are being implemented. However, there is a need for new drugs and rapid diagnostic methods. For this endeavour, in this paper, we present the syn...

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Autores principales: Maganti, Lakshmi Haritha Bharathi, Ramesh, Deepthi, Vijayakumar, Balaji Gowrivel, Khan, Mohd Imran K., Dhayalan, Arunkumar, Kamalraja, Jayabal, Kannan, Tharanikkarasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984819/
https://www.ncbi.nlm.nih.gov/pubmed/35424819
http://dx.doi.org/10.1039/d2ra00928e
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author Maganti, Lakshmi Haritha Bharathi
Ramesh, Deepthi
Vijayakumar, Balaji Gowrivel
Khan, Mohd Imran K.
Dhayalan, Arunkumar
Kamalraja, Jayabal
Kannan, Tharanikkarasu
author_facet Maganti, Lakshmi Haritha Bharathi
Ramesh, Deepthi
Vijayakumar, Balaji Gowrivel
Khan, Mohd Imran K.
Dhayalan, Arunkumar
Kamalraja, Jayabal
Kannan, Tharanikkarasu
author_sort Maganti, Lakshmi Haritha Bharathi
collection PubMed
description Mycobacterium tuberculosis resistance to commercially available drugs is increasing day by day. To address this issue, various strategies were planned and are being implemented. However, there is a need for new drugs and rapid diagnostic methods. For this endeavour, in this paper, we present the synthesis of acetylene containing 2-(2-hydrazinyl) thiazole derivatives and in vitro evaluation against the H37Rv strain of Mycobacterium tuberculosis. Among the developed 26 acetylene containing 2-(2-hydrazinyl) thiazole derivatives, eight compounds inhibited the growth of Mycobacterium tuberculosis with MIC values ranging from 100 μg ml(−1) to 50 μg ml(−1). The parent acetylene containing thiosemicarbazones showed promising antimycobacterial activity by inhibiting up to 75% of the Mycobacterium at 50 μg ml(−1). In addition, in silico studies were employed to understand the binding mode of all the novel acetylene-containing derivatives against the KasA protein of the Mycobacterium. Interestingly, the KasA protein interactions with the compounds were similar to the interactions of KasA protein with thiolactomycin and rifampicin. Cytotoxicity study results indicate that the compounds tested are non-toxic to human embryonic kidney cells.
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spelling pubmed-89848192022-04-13 Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis Maganti, Lakshmi Haritha Bharathi Ramesh, Deepthi Vijayakumar, Balaji Gowrivel Khan, Mohd Imran K. Dhayalan, Arunkumar Kamalraja, Jayabal Kannan, Tharanikkarasu RSC Adv Chemistry Mycobacterium tuberculosis resistance to commercially available drugs is increasing day by day. To address this issue, various strategies were planned and are being implemented. However, there is a need for new drugs and rapid diagnostic methods. For this endeavour, in this paper, we present the synthesis of acetylene containing 2-(2-hydrazinyl) thiazole derivatives and in vitro evaluation against the H37Rv strain of Mycobacterium tuberculosis. Among the developed 26 acetylene containing 2-(2-hydrazinyl) thiazole derivatives, eight compounds inhibited the growth of Mycobacterium tuberculosis with MIC values ranging from 100 μg ml(−1) to 50 μg ml(−1). The parent acetylene containing thiosemicarbazones showed promising antimycobacterial activity by inhibiting up to 75% of the Mycobacterium at 50 μg ml(−1). In addition, in silico studies were employed to understand the binding mode of all the novel acetylene-containing derivatives against the KasA protein of the Mycobacterium. Interestingly, the KasA protein interactions with the compounds were similar to the interactions of KasA protein with thiolactomycin and rifampicin. Cytotoxicity study results indicate that the compounds tested are non-toxic to human embryonic kidney cells. The Royal Society of Chemistry 2022-03-21 /pmc/articles/PMC8984819/ /pubmed/35424819 http://dx.doi.org/10.1039/d2ra00928e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Maganti, Lakshmi Haritha Bharathi
Ramesh, Deepthi
Vijayakumar, Balaji Gowrivel
Khan, Mohd Imran K.
Dhayalan, Arunkumar
Kamalraja, Jayabal
Kannan, Tharanikkarasu
Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title_full Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title_fullStr Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title_full_unstemmed Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title_short Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis
title_sort acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and in vitro and in silico evaluation of antimycobacterial activity against mycobacterium tuberculosis
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984819/
https://www.ncbi.nlm.nih.gov/pubmed/35424819
http://dx.doi.org/10.1039/d2ra00928e
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