title: Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.
abstract: 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.
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines; Institute of Pharmaceutical Sciences, National Institutes of Health, University of the Philippines Manila, Manila, Philippines.
authors.forename: Junie B
authors.initials: JB
authors.lastname: Billones
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Maria Constancia O
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Voltaire G
authors.initials: VG
authors.lastname: Organo
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Stephani Joy Y
authors.initials: SJ
authors.lastname: Macalino
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Jamie Bernadette A
authors.initials: JB
authors.lastname: Sy
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Inno A
authors.initials: IA
authors.lastname: Emnacen
authors.affiliation: Office of the Vice President for Academic Affairs - Emerging Interdisciplinary Research Program: "Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines," Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Nina Abigail B
authors.initials: NA
authors.lastname: Clavio
authors.affiliation: Marine Science Institute, University of the Philippines Diliman, Diliman, Quezon City, Philippines.
authors.forename: Gisela P
authors.initials: GP
authors.lastname: Concepcion
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D010458:Peptidyl Transferases
keywords: antituberculosis drug discovery; docking; virtual screening