title: Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.
abstract: A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation.
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India; Centre for Research and Development, Prist University, Thanjavur, Tamil Nadu 613 403, India.
authors.forename: Uttam A
authors.initials: UA
authors.lastname: More
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India. Electronic address: shrinivasdj@rediffmail.com.
authors.forename: Shrinivas D
authors.initials: SD
authors.lastname: Joshi
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India.
authors.forename: Tejraj M
authors.initials: TM
authors.lastname: Aminabhavi
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India.
authors.forename: Venkatrao H
authors.initials: VH
authors.lastname: Kulkarni
authors.affiliation: BDR Pharmaceuticals International Pvt. Ltd, Baroda, Gujarat, India.
authors.forename: Aravind M
authors.initials: AM
authors.lastname: Badiger
authors.affiliation: Université de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, LSPCMIB, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011758:Pyrroles
keywords: Anti-tubercular activity; Enoyl ACP reductase; Pharmacophore; Pyrrolyl phenoxy derivatives; Surflex-docking