Open Access
Antimicrobial Agents and Chemotherapy, volume 61, issue 11
Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis
Saqib Kidwai
1
,
Chan Yong Park
2, 3
,
Shradha Mawatwal
4
,
PRABHAKAR TIWARI
1
,
Myung Geun Jung
2
,
Tannu Priya Gosain
1
,
Pradeep Kumar
5
,
David Alland
5
,
Sandeep Kumar
6
,
Avinash Bajaj
6
,
Yun Kyung Hwang
2
,
Chang Sik Song
3
,
Rohan Dhiman
4
,
Ill Young Lee
2
,
Ramandeep Singh
1
1
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India
|
2
Eco-Friendly New Materials Research Centre, Korean Research Institute of Chemical Technology, Daejeon, South Korea
|
6
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India
|
Publication type: Journal Article
Publication date: 2017-11-05
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 4.9
ISSN: 00664804, 10986596
PubMed ID:
28893784
Pharmacology
Infectious Diseases
Pharmacology (medical)
Abstract
ABSTRACT New chemotherapeutic agents with novel mechanisms of action are urgently required to combat the challenge imposed by the emergence of drug-resistant mycobacteria. In this study, a phenotypic whole-cell screen identified 5-nitro-1,10-phenanthroline (5NP) as a lead compound. 5NP-resistant isolates harbored mutations that were mapped to fbiB and were also resistant to the bicyclic nitroimidazole PA-824. Mechanistic studies confirmed that 5NP is activated in an F420-dependent manner, resulting in the formation of 1,10-phenanthroline and 1,10-phenanthrolin-5-amine as major metabolites in bacteria. Interestingly, 5NP also killed naturally resistant intracellular bacteria by inducing autophagy in macrophages. Structure-activity relationship studies revealed the essentiality of the nitro group for in vitro activity, and an analog, 3-methyl-6-nitro-1,10-phenanthroline, that had improved in vitro activity and in vivo efficacy in mice compared with that of 5NP was designed. These findings demonstrate that, in addition to a direct mechanism of action against Mycobacterium tuberculosis, 5NP also modulates the host machinery to kill intracellular pathogens.
Top-30
Citations by journals
1
2
|
|
Frontiers in Microbiology
2 publications, 6.67%
|
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International Journal of Biological Macromolecules
2 publications, 6.67%
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Microbiology spectrum
2 publications, 6.67%
|
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Antimicrobial Agents and Chemotherapy
2 publications, 6.67%
|
|
Journal of Structural Chemistry
1 publication, 3.33%
|
|
Pharmaceuticals
1 publication, 3.33%
|
|
Frontiers in Cellular and Infection Microbiology
1 publication, 3.33%
|
|
Scientific Reports
1 publication, 3.33%
|
|
Results in Chemistry
1 publication, 3.33%
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Journal of Molecular Structure
1 publication, 3.33%
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Journal of Biological Chemistry
1 publication, 3.33%
|
|
Biochimica et Biophysica Acta - General Subjects
1 publication, 3.33%
|
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Drug Discovery Today
1 publication, 3.33%
|
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Bioorganic and Medicinal Chemistry Letters
1 publication, 3.33%
|
|
Cytokine
1 publication, 3.33%
|
|
IUBMB Life
1 publication, 3.33%
|
|
Journal of Biochemical and Molecular Toxicology
1 publication, 3.33%
|
|
Journal of Medicinal Chemistry
1 publication, 3.33%
|
|
MedChemComm
1 publication, 3.33%
|
|
RSC Advances
1 publication, 3.33%
|
|
Virulence
1 publication, 3.33%
|
|
Journal of Antimicrobial Chemotherapy
1 publication, 3.33%
|
|
Science advances
1 publication, 3.33%
|
|
Genetics and Molecular Biology
1 publication, 3.33%
|
|
1
2
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Citations by publishers
1
2
3
4
5
6
7
8
|
|
Elsevier
8 publications, 26.67%
|
|
American Society for Microbiology
4 publications, 13.33%
|
|
Frontiers Media S.A.
3 publications, 10%
|
|
Wiley
2 publications, 6.67%
|
|
Royal Society of Chemistry (RSC)
2 publications, 6.67%
|
|
Pleiades Publishing
1 publication, 3.33%
|
|
Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 3.33%
|
|
Springer Nature
1 publication, 3.33%
|
|
American Society for Biochemistry and Molecular Biology
1 publication, 3.33%
|
|
American Chemical Society (ACS)
1 publication, 3.33%
|
|
Taylor & Francis
1 publication, 3.33%
|
|
Oxford University Press
1 publication, 3.33%
|
|
American Association for the Advancement of Science (AAAS)
1 publication, 3.33%
|
|
Sociedade Brasileira de Genetica
1 publication, 3.33%
|
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1
2
3
4
5
6
7
8
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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GOST
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Kidwai S. et al. Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis // Antimicrobial Agents and Chemotherapy. 2017. Vol. 61. No. 11.
GOST all authors (up to 50)
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Kidwai S., Park C. Y., Mawatwal S., TIWARI P., Jung M. G., Gosain T. P., Kumar P., Alland D., Kumar S., Bajaj A., Hwang Y. K., Song C. S., Dhiman R., Lee I. Y., Singh R. Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis // Antimicrobial Agents and Chemotherapy. 2017. Vol. 61. No. 11.
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TY - JOUR
DO - 10.1128/aac.00969-17
UR - https://doi.org/10.1128/aac.00969-17
TI - Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis
T2 - Antimicrobial Agents and Chemotherapy
AU - Kidwai, Saqib
AU - Park, Chan Yong
AU - Mawatwal, Shradha
AU - TIWARI, PRABHAKAR
AU - Jung, Myung Geun
AU - Gosain, Tannu Priya
AU - Kumar, Pradeep
AU - Alland, David
AU - Kumar, Sandeep
AU - Bajaj, Avinash
AU - Hwang, Yun Kyung
AU - Song, Chang Sik
AU - Dhiman, Rohan
AU - Lee, Ill Young
AU - Singh, Ramandeep
PY - 2017
DA - 2017/11/05 00:00:00
PB - American Society for Microbiology
IS - 11
VL - 61
PMID - 28893784
SN - 0066-4804
SN - 1098-6596
ER -
Cite this
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@article{2017_Kidwai,
author = {Saqib Kidwai and Chan Yong Park and Shradha Mawatwal and PRABHAKAR TIWARI and Myung Geun Jung and Tannu Priya Gosain and Pradeep Kumar and David Alland and Sandeep Kumar and Avinash Bajaj and Yun Kyung Hwang and Chang Sik Song and Rohan Dhiman and Ill Young Lee and Ramandeep Singh},
title = {Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2017},
volume = {61},
publisher = {American Society for Microbiology},
month = {nov},
url = {https://doi.org/10.1128/aac.00969-17},
number = {11},
doi = {10.1128/aac.00969-17}
}