Cargando…

Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening

BACKGROUND: 7,8-Diaminopelargonic acid synthase (BioA), an enzyme of biotin biosynthesis pathway, is a well-known promising target for anti-tubercular drug development. METHODS: In this study, structure-based virtual screening was employed against the active site of BioA to identify new chemical ent...

Descripción completa

Detalles Bibliográficos
Autores principales: Singh, Swati, Khare, Garima, Bahal, Ritika Kar, Ghosh, Prahlad C, Tyagi, Anil K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935190/
https://www.ncbi.nlm.nih.gov/pubmed/29750019
http://dx.doi.org/10.2147/DDDT.S144240
_version_ 1783320255232212992
author Singh, Swati
Khare, Garima
Bahal, Ritika Kar
Ghosh, Prahlad C
Tyagi, Anil K
author_facet Singh, Swati
Khare, Garima
Bahal, Ritika Kar
Ghosh, Prahlad C
Tyagi, Anil K
author_sort Singh, Swati
collection PubMed
description BACKGROUND: 7,8-Diaminopelargonic acid synthase (BioA), an enzyme of biotin biosynthesis pathway, is a well-known promising target for anti-tubercular drug development. METHODS: In this study, structure-based virtual screening was employed against the active site of BioA to identify new chemical entities for BioA inhibition and top ranking compounds were evaluated for their ability to inhibit BioA enzymatic activity. RESULTS: Seven compounds inhibited BioA enzymatic activity by greater than 60% at 100 μg/mL with most potent compounds being A36, A35 and A65, displaying IC(50) values of 10.48 μg/mL (28.94 μM), 33.36 μg/mL (88.16 μM) and 39.17 μg/mL (114.42 μM), respectively. Compounds A65 and A35 inhibited Mycobacterium tuberculosis (M. tuberculosis) growth with MIC(90) of 20 μg/mL and 80 μg/mL, respectively, whereas compound A36 exhibited relatively weak inhibition of M. tuberculosis growth (83% inhibition at 200 μg/mL). Compound A65 emerged as the most potent compound identified in our study that inhibited BioA enzymatic activity and growth of the pathogen and possessed drug-like properties. CONCLUSION: Our study has identified a few hit molecules against M. tuberculosis BioA that can act as potential candidates for further development of potent anti-tubercular therapeutic agents.
format Online
Article
Text
id pubmed-5935190
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-59351902018-05-10 Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening Singh, Swati Khare, Garima Bahal, Ritika Kar Ghosh, Prahlad C Tyagi, Anil K Drug Des Devel Ther Original Research BACKGROUND: 7,8-Diaminopelargonic acid synthase (BioA), an enzyme of biotin biosynthesis pathway, is a well-known promising target for anti-tubercular drug development. METHODS: In this study, structure-based virtual screening was employed against the active site of BioA to identify new chemical entities for BioA inhibition and top ranking compounds were evaluated for their ability to inhibit BioA enzymatic activity. RESULTS: Seven compounds inhibited BioA enzymatic activity by greater than 60% at 100 μg/mL with most potent compounds being A36, A35 and A65, displaying IC(50) values of 10.48 μg/mL (28.94 μM), 33.36 μg/mL (88.16 μM) and 39.17 μg/mL (114.42 μM), respectively. Compounds A65 and A35 inhibited Mycobacterium tuberculosis (M. tuberculosis) growth with MIC(90) of 20 μg/mL and 80 μg/mL, respectively, whereas compound A36 exhibited relatively weak inhibition of M. tuberculosis growth (83% inhibition at 200 μg/mL). Compound A65 emerged as the most potent compound identified in our study that inhibited BioA enzymatic activity and growth of the pathogen and possessed drug-like properties. CONCLUSION: Our study has identified a few hit molecules against M. tuberculosis BioA that can act as potential candidates for further development of potent anti-tubercular therapeutic agents. Dove Medical Press 2018-05-01 /pmc/articles/PMC5935190/ /pubmed/29750019 http://dx.doi.org/10.2147/DDDT.S144240 Text en © 2018 Singh et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Singh, Swati
Khare, Garima
Bahal, Ritika Kar
Ghosh, Prahlad C
Tyagi, Anil K
Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title_full Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title_fullStr Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title_full_unstemmed Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title_short Identification of Mycobacterium tuberculosis BioA inhibitors by using structure-based virtual screening
title_sort identification of mycobacterium tuberculosis bioa inhibitors by using structure-based virtual screening
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935190/
https://www.ncbi.nlm.nih.gov/pubmed/29750019
http://dx.doi.org/10.2147/DDDT.S144240
work_keys_str_mv AT singhswati identificationofmycobacteriumtuberculosisbioainhibitorsbyusingstructurebasedvirtualscreening
AT kharegarima identificationofmycobacteriumtuberculosisbioainhibitorsbyusingstructurebasedvirtualscreening
AT bahalritikakar identificationofmycobacteriumtuberculosisbioainhibitorsbyusingstructurebasedvirtualscreening
AT ghoshprahladc identificationofmycobacteriumtuberculosisbioainhibitorsbyusingstructurebasedvirtualscreening
AT tyagianilk identificationofmycobacteriumtuberculosisbioainhibitorsbyusingstructurebasedvirtualscreening