Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis

Abstract The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an...

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Autores principales:	Md Imtiazul Islam, Hoonhee Seo, Sukyung Kim, Venkata S. Sadu, Kee-In Lee, Ho-Yeon Song
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8477fea70e9d4a79bda917dfb32f57c1
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spelling	oai:doaj.org-article:8477fea70e9d4a79bda917dfb32f57c12021-12-02T15:23:07ZAntimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis10.1038/s41598-020-80227-y2045-2322https://doaj.org/article/8477fea70e9d4a79bda917dfb32f57c12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80227-yhttps://doaj.org/toc/2045-2322Abstract The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an isoindole based chemical library and screened a potential candidate with significant anti-tuberculosis activity. The compound named 2-hydroxy-4-(4-nitro-1,3-dioxoisoindolin-2-yl) benzoic acid (IDD-B40) showed strong activity against all the tested drug-susceptible and drug-resistant strains of M. tuberculosis, with the 50% minimum inhibitory concentrations (MIC50) of 0.39 μg/ml both in culture broth and inside Raw 264.7 cells. Also, IDD-B40, in combination with rifampicin, exhibited a direct synergistic effect against both XDR and H37Rv M. tuberculosis. Besides, IDD-B40 showed a better post-antibiotic effect (PAE) than did some first-line drugs and showed no significant cytotoxicity to any cell line tested, with a selectivity index of ≥ 128. Although IDD-B40 showed a result similar to isoniazid in the preliminary mycolic acid inhibition assay, it did not exhibit any effect against other mycolic acid-producing nontuberculous mycobacterial strains (NTM), and different non-mycobacterial pathogenic strains, so further studies are required to confirm the mode of action of IDD-B40. Considering its results against M. tuberculosis, IDD-B40 is a potential anti-tuberculosis drug candidate. However, further studies are required to evaluate its potential in vivo effect and therapeutic potential.Md Imtiazul IslamHoonhee SeoSukyung KimVenkata S. SaduKee-In LeeHo-Yeon SongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Md Imtiazul Islam Hoonhee Seo Sukyung Kim Venkata S. Sadu Kee-In Lee Ho-Yeon Song Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
description	Abstract The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an isoindole based chemical library and screened a potential candidate with significant anti-tuberculosis activity. The compound named 2-hydroxy-4-(4-nitro-1,3-dioxoisoindolin-2-yl) benzoic acid (IDD-B40) showed strong activity against all the tested drug-susceptible and drug-resistant strains of M. tuberculosis, with the 50% minimum inhibitory concentrations (MIC50) of 0.39 μg/ml both in culture broth and inside Raw 264.7 cells. Also, IDD-B40, in combination with rifampicin, exhibited a direct synergistic effect against both XDR and H37Rv M. tuberculosis. Besides, IDD-B40 showed a better post-antibiotic effect (PAE) than did some first-line drugs and showed no significant cytotoxicity to any cell line tested, with a selectivity index of ≥ 128. Although IDD-B40 showed a result similar to isoniazid in the preliminary mycolic acid inhibition assay, it did not exhibit any effect against other mycolic acid-producing nontuberculous mycobacterial strains (NTM), and different non-mycobacterial pathogenic strains, so further studies are required to confirm the mode of action of IDD-B40. Considering its results against M. tuberculosis, IDD-B40 is a potential anti-tuberculosis drug candidate. However, further studies are required to evaluate its potential in vivo effect and therapeutic potential.
format	article
author	Md Imtiazul Islam Hoonhee Seo Sukyung Kim Venkata S. Sadu Kee-In Lee Ho-Yeon Song
author_facet	Md Imtiazul Islam Hoonhee Seo Sukyung Kim Venkata S. Sadu Kee-In Lee Ho-Yeon Song
author_sort	Md Imtiazul Islam
title	Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
title_short	Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
title_full	Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
title_fullStr	Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
title_full_unstemmed	Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
title_sort	antimicrobial activity of idd-b40 against drug-resistant mycobacterium tuberculosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8477fea70e9d4a79bda917dfb32f57c1
work_keys_str_mv	AT mdimtiazulislam antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis AT hoonheeseo antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis AT sukyungkim antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis AT venkatassadu antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis AT keeinlee antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis AT hoyeonsong antimicrobialactivityofiddb40againstdrugresistantmycobacteriumtuberculosis
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Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis

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