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Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of...

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Autores principales: Haroun, Michelyne, Tratrat, Christophe, Petrou, Anthi, Geronikaki, Athina, Ivanov, Marija, Ćirić, Ana, Soković, Marina, Nagaraja, Sreeharsha, Venugopala, Katharigatta Narayanaswamy, Balachandran Nair, Anroop, Elsewedy, Heba S., Kochkar, Hafedh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271899/
https://www.ncbi.nlm.nih.gov/pubmed/34279400
http://dx.doi.org/10.3390/molecules26134061
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author Haroun, Michelyne
Tratrat, Christophe
Petrou, Anthi
Geronikaki, Athina
Ivanov, Marija
Ćirić, Ana
Soković, Marina
Nagaraja, Sreeharsha
Venugopala, Katharigatta Narayanaswamy
Balachandran Nair, Anroop
Elsewedy, Heba S.
Kochkar, Hafedh
author_facet Haroun, Michelyne
Tratrat, Christophe
Petrou, Anthi
Geronikaki, Athina
Ivanov, Marija
Ćirić, Ana
Soković, Marina
Nagaraja, Sreeharsha
Venugopala, Katharigatta Narayanaswamy
Balachandran Nair, Anroop
Elsewedy, Heba S.
Kochkar, Hafedh
author_sort Haroun, Michelyne
collection PubMed
description Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF(3)-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF(3) substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.
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spelling pubmed-82718992021-07-11 Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation Haroun, Michelyne Tratrat, Christophe Petrou, Anthi Geronikaki, Athina Ivanov, Marija Ćirić, Ana Soković, Marina Nagaraja, Sreeharsha Venugopala, Katharigatta Narayanaswamy Balachandran Nair, Anroop Elsewedy, Heba S. Kochkar, Hafedh Molecules Article Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF(3)-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF(3) substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds. MDPI 2021-07-02 /pmc/articles/PMC8271899/ /pubmed/34279400 http://dx.doi.org/10.3390/molecules26134061 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haroun, Michelyne
Tratrat, Christophe
Petrou, Anthi
Geronikaki, Athina
Ivanov, Marija
Ćirić, Ana
Soković, Marina
Nagaraja, Sreeharsha
Venugopala, Katharigatta Narayanaswamy
Balachandran Nair, Anroop
Elsewedy, Heba S.
Kochkar, Hafedh
Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title_full Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title_fullStr Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title_full_unstemmed Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title_short Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
title_sort exploration of the antimicrobial effects of benzothiazolylthiazolidin-4-one and in silico mechanistic investigation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271899/
https://www.ncbi.nlm.nih.gov/pubmed/34279400
http://dx.doi.org/10.3390/molecules26134061
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