Chemoinformatics approach to the screening and development of quassinoids from Brucea javanica as antituberculosis drugs

Abstract

Background: The morbidity and mortality of tuberculosis (TB) remain high in various countries as a result of pharmacological intervention failures, such as incomplete treatment regimens and inadequate doses, triggering resistance of Mycobacterium tuberculosis strains to anti-TB drugs used. This phenomenon requires innovation to explore and develop novel anti-TB drugs so that the problem of resistance is overcome and treatment of TB is more optimal. Objective: In this study, chemoinformatics investigations were carried out on quassinoids derived from Brucea javanica to be developed as anti-TB drugs. Method: Evaluation of drug-likeness with the SwissADME online tool, prediction of toxicity with the pkCSM online tool, and molecular docking studies with AutoDock Vina software were performed on 18 quassinoids from Brucea javanica. Result: The findings showed that Bruceine A, Bruceine, and Bruceine D, met the drug-likeness criteria, showed a good toxicity profile, and had better binding energy (-7.5; -7.5; and -7 kcal/mol, respectively) than isoniazid (-5.8 kcal/mol) which is a first-line anti-TB drug on enoyl acyl carrier protein reductase (InhA; PDB ID: 2NSD). Conclusion: This study found several quassinoids from Brucea javanica with the potential to be developed as anti-TB drugs.