Pyridine and quinoline molecules as crucial protagonists in the never-stopping discovery of new agents against tuberculosis

Abstract

Tuberculosis (TB) disease remains to be an alarming infection worldwide with nearly 1.6 million deaths per year ranking above HIV/AIDS. Although Mycobacterium tuberculosis (Mtb), which causes TB, was identified more than 130 years ago, nowadays only old vaccine (Bacillus Calmette-Guérin vaccine) and classical toxic drugs that are losing its effectiveness are available in clinic practice. Despite enormous efforts in drug research on TB treatment including vaccines and diagnostics investigations, this old contagious, infectious disease is still a major public health problem. The goal of elimination of epidemic TB disease by 2035 will not be achieved without combined strategies based on faster diagnostic tools, effective vaccines and drugs. In the field of TB chemotherapy, novel molecular design of new compounds able to efficiently kill Mtb via a disruption of new diverse biological targets is evidently required. In this sense, pyridine and quinoline compounds stand out as promising molecules against drug-resistant tuberculosis. Indeed, many candidate drugs based on heterocyclic skeletons are currently being tested. Among them, quinoline derivatives like gatifloxacin, moxifloxacin and bedaquiline (sirturo), and pyridine molecules such as sudoterb and agent BRD-8000.3 have been shown to have high potential for more effective treatment of the drug-resistant forms of TB disease. In this work we review the most significant advances in the design of such molecules discussing briefly their physicochemical parameters (descriptors) calculated by available Molinspiration software.

Keywords: Anti-antitubercular drugs; Bedaquiline; Isoniazid; Lipinski' parameters, in silico study; Mycobacterium tuberculosis; Pyridines; Quinolines.