Virtual screening against mycobacterium tuberculosis lipoate protein ligase B (MtbLipB) and in silico ADMET evaluation of top hits

• Main Authors: Billones, Junie B., Carrillo, Maria Constancia O., Organo, Voltaire G., Macalino, Stephani Joy Y., Emnacen, Inno A., Sy, Jamie Bernadette A.
• Format: text
• Published: Animo Repository 2013
• Subjects: Mycobacterium tuberculosis; Antitubercular agents; Medicinal-Pharmaceutical Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11461
• Institution: De La Salle University

The emergence of drug resistant strains of Mycobacterium tuberculosis(Mtb) has spurred the search for new therapeutic targets for the development of more efficient anti-tuberculosis drugs. Lipoate protein ligase B (LipB), an enzyme involved in the biosynthesis of the lipoic acid cofactor, is considered as a very promising drug target in M. tuberculosis, since the bacteria has no known substitute enzyme that can take over the role of LipB in its metabolic system. Hence, apharmacophore-based screening, docking, and ADMET evaluation of compounds obtained from the National Cancer Institute (NCI) Database were performed against the MtbLipB enzyme. Consequently,nine compounds with superior binding energies compared to its known inhibitor (decanoic acid) have been identified. Moreover, among these nine compounds, NSC164080 (methyl 2-(2-(((benzyloxy)carbonyl)amino)propanamido)- 3-(4-hydroxyphenyl)propanoate) displayed the most favorable ADMETproperties. The results in this work may pave the way for the development of a novel class of antituberculosis agents.