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

doi:10.4155/fmc-2018-0039

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

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10 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 language	English (US)
Pages (from-to)	1787-1804
Number of pages	18
Journal	Future Medicinal Chemistry
Volume	10
Issue number	15
DOIs	https://doi.org/10.4155/fmc-2018-0039
State	Published - 2018

Keywords

QSAR
bronchodilator
conjugate
indole
molecular modeling
pharmacophore
pyridine

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Drug Discovery

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title = "Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates",

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.",

keywords = "QSAR, bronchodilator, conjugate, indole, molecular modeling, pharmacophore, pyridine",

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

note = "Publisher Copyright: {\textcopyright} 2018 Newlands Press.",

year = "2018",

doi = "10.4155/fmc-2018-0039",

language = "English (US)",

volume = "10",

pages = "1787--1804",

journal = "Future Medicinal Chemistry",

issn = "1756-8919",

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T1 - Synthesis & molecular modeling studies of bronchodilatory active indole-pyridine conjugates

AU - Srour, Aladdin M.

AU - Panda, Siva S.

AU - M Salman, Asmaa M.

AU - El-Manawaty, May A.

AU - George, Riham F.

AU - Shalaby, Elsayed M.

AU - Fitch, Andrew N.

AU - Fawzy, Nehmedo G.

AU - Girgis, Adel S.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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