Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

Autor:	Elzahhar PA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Elkazaz S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Soliman R; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., El-Tombary AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Shaltout HA; Department of Obstetrics & Gynecology, School of Medicine, Wake Forest University, NC 27157, USA., El-Ashmawy IM; Department of Pharmacology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.; Department of Veterinary Medicine, Faculty of Agricultural & Veterinary Medicine, Qassim University, P.O. Box 1482, Buraydah, Al-Qassim, Saudi Arabia., Abdel Wahab AE; Genetic Engineering & Biotechnology Research Institute (GEBRI), The City of Scientific Research & Technology Applications (SRTA-City), Borg El-Arab, Alexandria, Egypt., El-Hawash SA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Jazyk:	angličtina
Zdroj:	Future medicinal chemistry [Future Med Chem] 2017 Aug; Vol. 9 (12), pp. 1413-1450. Date of Electronic Publication: 2017 Aug 03.
DOI:	10.4155/fmc-2017-0071
Abstrakt:	Aim: Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. Results: This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. Conclusion: This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.
Databáze:	MEDLINE
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