Title : Synthetic quinolines and related heterocycles in the discovery of new agents against M. tuberculosis and NTM
Abstract:
Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis (Mtb), is still one of the world's greatest threats. Ending the TB epidemic by 2030 is among the health aims of the United Nations Sustainable Development Goals (SDGs). Moreover, the incidence and number of deaths from nontuberculous mycobacterial disease (NTM) have been steadily increasing globally and these mycobacteria have become extremely resistant to antibiotics and are easily dispersed by migration and climate change. Our research group has been developing quinoline derivatives with anti-TB activity for more than fifteen years. Although initially targeted as antimalarial agents, the design was focused on anti-TB activity, inspired by natural active alkaloids. The discovery of bedaquiline and its approval by the FDA was the driving force to design new 2,4-diarylquinolines as well as polycyclic and fused quinolines. To design new antituberculosis agents with a quinoline structure, our group developed three-dimensional structure-activity relationship (3D-QSAR) models, based on Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). These models were used to find the key structural features and design fifteen new compounds prepared via the MW-assisted Friedländer reaction in good yields, with inhibition growth activity against M. tuberculosis. In addition, was explored the potential application of the designed compounds as growth inhibitors on resistant M. tuberculosis culture, as well as against non-tuberculosis culture among them M. avium and M. abscessus.
Audience Take-Away:
- Yes, this research is such that other faculty could use to expand their research or teaching
- Yes, it will improve the accuracy of a design, or provide new information to assist in a design problem
- Knowing about tuberculosis and nontuberculous mycobacterial disease (NTM), discovery of hit anti-TB compounds.
