Identification of potential compounds for the management of multidrug-resistant tuberculosis using computational methods

Abstract

Background: Tuberculosis is caused by Mycobacterium tuberculosis and is spread through the air. Multidrug-resistant tuberculosis (MDR TB) has become a global health concern. This study focuses on developing alternative compounds to Levofloxacin, Moxifloxacin, Bedaquiline, Kanamycin, Amikacin, Cycloserine, Ethambutol, Pyrazinamide, Linezolid and Streptomycin that can be used to treat patients with multidrug resistance TB. The virtual screening will aid in discovering other possible compounds for use in the management of MDR TB, thereby providing a superior alternative to currently existing medications and aid in eradicating TB. The objective of this study was to identify potential compounds that can be used in managing MDR TB in chronic tuberculosis patients using computational methods. Methods: The Swiss Similarity tool was used to identify similar compounds to the tuberculosis drugs in a ZINC database. Compounds more similar to the tuberculosis drugs were selected and used to test the molecular docking with their respective targets. The pharmacokinetics and toxicity profiles of the selected compounds were analyzed using Swiss ADME and Pro Tox Server, respectively. Results: Overall, 90 compounds had higher binding energies than the medications, 88 had lower binding energies, and 14 had binding energies that were equivalent to those of the drugs. Only 14 of the 200 compounds lacked CYP inhibition, were p-glycoprotein substrates, had superior docking scores to the compounds, and fell into toxicity classes V and VI. Conclusions: The 14 potential compounds should undergo further in vivo and in vitro studies to develop new compounds for managing multidrug-resistant tuberculosis.