A novel vitamin C analog acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. We investigated the use of vitamin C-derived isotetrones as bio- enhancer agents. In this context, our results revealed that the lead compound C11 inhibits growth, improves MIC/MBC, and enhances the killing of M. tuberculosis H37Rv strain when used in combination with first-line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduced the generation of spontaneous mutants against rifampicin and reached a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds were proven to be effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We also found that C11 induced the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.