Identification of megacerotonic acid and a quinazoline derivative from Universal Natural Product Database as potential inhibitors of Trypanosoma brucei brucei alternative oxidase: molecular docking, molecular dynamic simulation and MM/PBSA analysis.

ABSTRACT: African trypanosomiasis is caused by Trypanosoma brucei subspecies and available drugs against it, are unsatisfactory due to poor pharmacokinetic properties. Trypanosomal Alternative Oxidase (TAO) is an attractive target for anti-trypanosome rational drug discovery because it is essential for parasite-specific ATP generation and absent in the mammalian host. In this study, 360 filtered ligands from the Universal Natural Product Database were virtually screened and docked on T. brucei brucei TAO (PDB-ID 3VVA). From the virtual screening, 10 ligands with binding energy from -10.6 to -9.0 kcal/mol were selected as hits and further subjected pharmacokinetic and toxicity analyses where all of them passed Lipinski's rule of five. Also, the compounds were non-mutagenic, non-tumorige

SUBMITTER: Adamu RM 

PROVIDER: S-EPMC9148700 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature