Design, synthesis, anti-inflammatory antitumor activities, molecular modeling and molecular dynamics simulations of potential naprosyn® analogs as COX-1 and/or COX-2 inhibitors.

Autor: El Sayed MT; Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt. Electronic address: mardia.elsayed2016@gmail.com., El-Sharief MAMS; Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt., Zarie ES; Department of Chemotherapy, National Research Centre, 12622 Dokki, Egypt; Material Science Department, Aalto University, Kemistintie 1, 00076 Aalto, Finland., Morsy NM; Deparment of Organometallic and Organometalloid Chemistry, National Research Centre, 12622 Dokki, Egypt., Elsheakh AR; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt., Nayel M; National Cancer Institute, Chemotherapeutic Agents Repository, Fisher BioServices, Germantown, MD 20874, USA., Voronkov A; Digital Bio Pharm Ltd., 145-157 St. John Street, London EC1V 4PW, UK., Berishvili V; Department of Chemistry, Lomonosov Moscow State University, 1/3, Moscow 119991, Russia., Sabry NM; Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt., Hassan GS; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt. Electronic address: ghadak25@yahoo.com., Abdel-Aziz HA; Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2018 Feb; Vol. 76, pp. 188-201. Date of Electronic Publication: 2017 Nov 13.
DOI: 10.1016/j.bioorg.2017.11.002
Abstrakt: Inflammation is a fundamental physiological process that is essential for survival of human being but at the same time is one of the major causes of human morbidity and mortality. In the past decade, numerous advances have taken place in the understanding and development of novel anti-inflammatory drugs. Therefore, investigation of newest anti-inflammatory agents is still a major challenge. In this study, novel and successfully synthesized naproxen-derivatives indicated powerful anti-inflammatory properties as potent of COX-1 and/or COX-2 inhibitors are reported. Results obtained revealed the presence of very potent derivatives with% inhibition of the oedema by 100% in addition to enzyme inhibition values that can reach 92%. The molecular docking and molecular dynamic calculations have been studied. Thus, new potent candidates for further investigation as prospective non-steroidal anti-inflammatory drug were proposed. Furthermore, twenty of the synthesized derivatives have been selected by the NCI, USA for anti-cancer screening and some of the tested compounds showed good% growth inhibition and some selectivity against some cell lines such as melanoma, non-small cell lung and colon cancer with GI% values ranging from 60.9 to 82.8%. Structure activity relationship has been performed and molecular modeling studies and molecular dynamic simulations have been performed for more explanation of the action of the synthesized compounds.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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