Toward antituberculosis drugs: In silico screening of synthetic compounds against Mycobacterium tuberculosis L,D-transpeptidase 2

• Main Authors: Billones, Junie B., Carrillo, Maria Constancia O., Organo, Voltaire G., Macalino, Stephani Joy Y., Sy, Jamie Bernadette A., Emnacen, Inno A., Clavio, Nina Abigail B., Concepcion, Gisela P.
• Format: text
• Published: Animo Repository 2016
• Subjects: Antitubercular agents; Mycobacterium tuberculosis; Medicinal-Pharmaceutical Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11460
• Institution: De La Salle University

Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme l,d- transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3→3 cross-linkages that make up the mycolyl–arabinogalactan–peptidoglycan complex of Mtb. In this study, structure-based pharmacophore screening, molecular docking, and in silico toxicity evaluations were employed in screening compounds from a database of synthetic compounds. Out of the 4.5 million database compounds, 18 structures were identified as high-scoring, high- binding hits with very satisfactory absorption, distribution, metabolism, excretion, and toxicity properties. Two out of the 18 compounds were further subjected to in vitro bioactivity assays, with one exhibiting a good inhibitory activity against the Mtb H37Ra strain.