Aladdin M Srour1, Siva S Panda2, Asmaa M M Salman3, May A El-Manawaty4, Riham F George5, ElSayed M Shalaby6, Andrew N Fitch7, Nehmedo G Fawzy8, Adel S Girgis8. 1. Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza 12622, Egypt. 2. Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA. 3. Medicinal & Pharmaceutical Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt. 4. Pharmacognosy Department, National Research Centre, Dokki, Giza 12622, Egypt. 5. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. 6. X-Ray Crystallography Laboratory, Physics Division, National Research Centre, Dokki, Giza 12622, Egypt. 7. European Synchrotron Radiation Facility, CS40220, 38043 Grenoble Cedex 9, France. 8. Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
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.
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.
Authors: Siva S Panda; Adel S Girgis; Bibhuti B Mishra; Mohamed Elagawany; Venkatasai Devarapalli; William F Littlefield; Ahmed Samir; Walid Fayad; Nehmedo G Fawzy; Aladdin M Srour; Riham M Bokhtia Journal: RSC Adv Date: 2019-07-01 Impact factor: 4.036