Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates

Aladdin M. Srour, Siva S. Panda, Asmaa M. M Salman, May A. El-Manawaty, Riham F. George, Elsayed M. Shalaby, Andrew N. Fitch, Nehmedo G. Fawzy, Adel S. Girgis

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Aim: Synthesis of novel bronchodilatory active indole-pyridine conjugates. Results/methodology: Indole-pyridine conjugates (6a-n, 8a-i and 10a-c) were synthesized in a facile pathway through reaction of 2-[(1-alkyl-1H-indol-3-yl)methylene]malononitriles 4a,b with the corresponding ketone-containing compounds (5a-f, 7a-c and 9a,b) in the presence of sodium alkoxide. Single (6l, 8 g) and powder (6k, 8d) x-ray studies supported the structures. Results: Histamine precontracted isolated tracheal rings of Guinea pig exhibited the potent bronchodilation properties of 6c (about double-fold potency relative to the standard reference, theophylline). Some of the synthesized conjugates (8d, 6c, 6f and 6e) revealed promising reduction of IL-8 production during lipopolysaccharide-induced airway inflammatory bioassay. Computational studies (3D pharmacophore, 2D-QSAR 'quantitative structure-activity relationship') showed high approximations to the bronchodilation properties and explained the parameters controlling biological observations.

Original languageEnglish (US)
Pages (from-to)1787-1804
Number of pages18
JournalFuture Medicinal Chemistry
Volume10
Issue number15
DOIs
StatePublished - 2018

Keywords

  • QSAR
  • bronchodilator
  • conjugate
  • indole
  • molecular modeling
  • pharmacophore
  • pyridine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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