title: Pharmacophore based virtual screening, synthesis and SAR of novel inhibitors of Mycobacterium sulfotransferase.
abstract: A planned 3D-pharmacophore mapping was carried out on the basis of chemical features associated with known Stf0 inhibitors. Four models (model 1-4) were obtained after GASP (Genetic Algorithm Similarity Program) refinement of seven models (D-1 to D-7) generated by using DISCOtech. The selected GASP model-1 has two hydrogen bond acceptor, two hydrogen bond donor and four hydrophobic points. This model was used for virtual screening (VS) of large public databases along with in house generated knowledge base database. VS followed by docking of selected compounds on Stf0 active site was carried and pose analysis done. Seven hits were identified after all the computational studies, of which 2 hits were synthesized along with their analogs and evaluated for antitubercular activity. IH-45 was found promising after in vitro assay.
authors.affiliation: Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Rikta
authors.initials: R
authors.lastname: Saha
authors.affiliation: Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Omprakash
authors.initials: O
authors.lastname: Tanwar
authors.affiliation: Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: M Mumtaz
authors.initials: MM
authors.lastname: Alam
authors.affiliation: Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Zaman
authors.affiliation: Department of Pharmacy, Oman Medical College, Muscat, Oman.
authors.forename: Shah A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India; Bioinformatics Facility, Jamia Hamdard, New Delhi 110062, India. Electronic address: mymoonaakhter@gmail.com.
authors.forename: Mymoona
authors.initials: M
authors.lastname: Akhter
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D009161:Mycobacterium / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D015238:Sulfotransferases
keywords: Anti-tubercular agents; Pharmacophore mapping; Sulfotransferase; Virtual screening