title: High throughput screening of 7-methylpicene-1,2-diol as arylamine N-acetyltransferase (NAT) inhibitor to establish a isoniazid supplement in anti-tubercular therapy.
abstract: Mycobacterium tuberculosis (Mtb), due to its unusual organization crosses different immune barriers and causes tuberculosis. The advent of multidrug resistance tuberculosis (MDR-TB) has attained alarming situation. Hence, computational drug design has been performed in this work to find potent molecules for this purpose. Isoniazid is a widely used frontline drug against tuberculosis. But reports justified the inactivity of isoniazid on acetylation by Arylamine N-acetyltransferase (NAT). 35 countries were highlighted to have isoniazid resistance from survey in 1998. Hence, Mtb NAT has been selected as the target in the present case and hundred compounds were screened in order to find potent NAT inhibitor to raise the efficacy of isoniazid. Molecular docking with Biosolveit LeadIT and Autodock 4.2 simulation was performed. The result showed 7- methylpicene-1, 2-diol to have -26.77 and -8.26 kcal/mol score in LeadIT and Autodock 4.2. The work validated 7- methylpicene-1, 2-diol to be a potent NAT inhibitor to supplement isoniazid.
authors.affiliation: Bioinformatics Centre (DBTBIF), Assam University Silchar, Assam 788011, India. abhishek@bioinfoaus.ac.in.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Paulomi
authors.initials: P
authors.lastname: Paul
authors.forename: Manabendra Dutta
authors.initials: MD
authors.lastname: Choudhury
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002911:Chrysenes / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007538:Isoniazid / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: C587031:7-methylpicene-1,2-diol; D000995:Antitubercular Agents; D002911:Chrysenes; D001191:Arylamine N-Acetyltransferase; D007538:Isoniazid