Home
Resources
Publications
Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline Against Mycobacterium Tuberculosis

Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline Against Mycobacterium Tuberculosis

Saqib Kidwai, Chan-Yong Park, Shradha Mawatwal, Prabhakar Tiwari, Myung Geun Jung, Tannu Priya Gosain, Pradeep Kumar, David Alland, Sandeep Kumar, Avinash Bajaj, Yun-Kyung Hwang, Chang Sik Song, Rohan Dhiman, etc.

Antimicrob Agents Chemother. 2017 Oct 24;61(11):e00969-17.

PMID: 28893784

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP4199886	5-Nitro-1,10-phenanthroline		4199-88-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: