Title:Virtual Screening Against M. tuberculosis 7,8-Diaminopelargonic Acid Synthase (MtbBioA) and In Silico Toxicity Evaluation of Top Hits
Volume: 10
Issue: 2
Author(s): Junie Billones, Maria C. Carrillo, Voltaire Organo, Stephani J. Macalino, Inno Emnacen and Jamie B. Sy
Affiliation:
Keywords:
ADMET, DAPA, 7, 8-Diaminopelargonic acid synthase (BioA), 7-Keto-8-aminopelargonic acid (KAPA), molecular
docking, Mycobacterium tuberculosis (Mtb), pharmacophore, virtual screening.
Abstract: Tuberculosis (TB) remains to be one of the major public health concerns worldwide. The continuing emergence
of Mtb strains resistant to known drugs makes the campaign for successful TB control and treatment very difficult to accomplish.
It is therefore imperative to search for newer chemical entities that could inhibit the growing number of putative
drug targets for the development of more efficient anti-tubercular drugs. One such ideal target is the 7, 8-
diaminopelargonic acid aminotransferase enzyme (BioA). This enzyme is mainly involved in the bacterium’s lipid biosynthesis
and metabolism machinery, and is considered as a very promising target due to the fact that humans lack this enzyme.
In this study, structure-based pharmacophore screening, molecular docking, and ADMET evaluation of compounds
obtained from the InterBioScreen Synthetic Compounds (IBS SC) were performed against the MtbBioA enzyme. Five
compounds from the library showed more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin
(ACM). Moreover, a pyridazinyladamantane 2-carboxylic acid and two sulfone derivatives have indicated
good ADMET properties. These compounds are predicted to possess desirable properties of a lead and should be the subject
of subsequent structural optimization and experimental bioactivity evaluations.
