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

Aladdin M. Srour, Siva Shankar 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 journalArticle

5 Citations (Scopus)

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 - Jan 1 2018

Fingerprint

Quantitative Structure-Activity Relationship
Theophylline
Ketones
Interleukin-8
Biological Assay
Powders
Histamine
Lipopolysaccharides
Guinea Pigs
Sodium
X-Rays
pyridine
indole
dicyanmethane

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Srour, A. M., Panda, S. S., M Salman, A. M., El-Manawaty, M. A., George, R. F., Shalaby, E. M., ... Girgis, A. S. (2018). Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates. Future Medicinal Chemistry, 10(15), 1787-1804. https://doi.org/10.4155/fmc-2018-0039

Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates. / Srour, Aladdin M.; Panda, Siva Shankar; M Salman, Asmaa M.; El-Manawaty, May A.; George, Riham F.; Shalaby, Elsayed M.; Fitch, Andrew N.; Fawzy, Nehmedo G.; Girgis, Adel S.

In: Future Medicinal Chemistry, Vol. 10, No. 15, 01.01.2018, p. 1787-1804.

Research output: Contribution to journalArticle

Srour, AM, Panda, SS, M Salman, AM, El-Manawaty, MA, George, RF, Shalaby, EM, Fitch, AN, Fawzy, NG & Girgis, AS 2018, 'Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates', Future Medicinal Chemistry, vol. 10, no. 15, pp. 1787-1804. https://doi.org/10.4155/fmc-2018-0039
Srour, Aladdin M. ; Panda, Siva Shankar ; M Salman, Asmaa M. ; El-Manawaty, May A. ; George, Riham F. ; Shalaby, Elsayed M. ; Fitch, Andrew N. ; Fawzy, Nehmedo G. ; Girgis, Adel S. / Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates. In: Future Medicinal Chemistry. 2018 ; Vol. 10, No. 15. pp. 1787-1804.
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