Saravanan, P and Dusthackeer, VNA and Rajmani, RS and Mahizhaveni, B and Nirmal, CR and Rajadas, SE and Bhardwaj, N and Ponnuraja, C and Bhaskar, A and Hemanthkumar, AK and Ramachandran, G and Tripathy, SP (2021) Discovery of a highly potent novel rifampicin analog by preparing a hybrid of the precursors of the antibiotic drugs rifampicin and clofazimine. In: Scientific Reports, 11 (1).
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Abstract
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). The present work reports the design and synthesis of a hybrid of the precursors of rifampicin and clofazimine, which led to the discovery of a novel Rifaphenazine (RPZ) molecule with potent anti-TB activity. In addition, the efficacy of RPZ was evaluated in-vitro using the reference strain Mtb H37Rv. Herein, 2,3 diamino phenazine, a precursor of an anti-TB drug clofazimine, was tethered to the rifampicin core. This 2,3 diamino phenazine did not have an inherent anti-TB activity even at a concentration of up to 2 µg/mL, while rifampicin did not exhibit any activity against Mtb at a concentration of 0.1 µg/mL. However, the synthesized novel Rifaphenzine (RPZ) inhibited 78 of the Mtb colonies at a drug concentration of 0.1 µg/mL, while 93 of the bacterial colonies were killed at 0.5 µg/mL of the drug. Furthermore, the Minimum Inhibitory Concentration (MIC) value for RPZ was 1 µg/mL. Time-kill studies revealed that all bacterial colonies were killed within a period of 24 h. The synthesized novel molecule was characterized using high-resolution mass spectroscopy and NMR spectroscopy. Cytotoxicity studies (IC50) were performed on human monocytic cell line THP-1, and the determined IC50 value was 96 µg/mL, which is non-cytotoxic. © 2021, The Author(s).
| Item Type: | Journal Article |
|---|---|
| Publication: | Scientific Reports |
| Publisher: | Nature Research |
| Additional Information: | Copyright to this article belongs to Nature Research |
| Department/Centre: | Division of Biological Sciences > Centre for Infectious Disease Research |
| Date Deposited: | 09 Feb 2021 07:44 |
| Last Modified: | 09 Feb 2021 07:44 |
| URI: | http://eprints.iisc.ac.in/id/eprint/67851 |
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