2. Academic Validation
  3. Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach

Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach

  • Eur J Med Chem. 2015 Apr 13:94:317-39. doi: 10.1016/j.ejmech.2015.03.013.
Uttam A More 1,  Shrinivas D Joshi 2,  Tejraj M Aminabhavi 3,  Venkatrao H Kulkarni 3,  Aravind M Badiger 4,  Christian Lherbet 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India.
  • 4 BDR Pharmaceuticals International Pvt. Ltd, Baroda, Gujarat, India.
  • 5 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.
PMID: 25771110 DOI: 10.1016/j.ejmech.2015.03.013
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.

Keywords

Anti-tubercular activity; Enoyl ACP reductase; Pharmacophore; Pyrrolyl phenoxy derivatives; Surflex-docking.

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