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

Research output: Contribution to journalArticleScientificpeer-review

Researchers

  • Mardia T. El Sayed
  • Marwa A.M.Sh El-Sharief
  • Eman Zarie

  • Nesrin M. Morsy
  • Ahmed R. Elsheakh
  • Mohammed Nayel
  • Andrey Voronkov
  • Vladimir Berishvili
  • Nermien M. Sabry
  • Ghada S. Hassan
  • Hatem A. Abdel-Aziz

Research units

  • National Research Center
  • Mansoura University
  • National Institutes of Health
  • Lomonosov Moscow State University
  • Digital Bio Pharm Ltd.

Abstract

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.

Details

Original languageEnglish
Pages (from-to)188-201
Number of pages14
JournalBioorganic Chemistry
Volume76
Publication statusPublished - 1 Feb 2018
MoE publication typeA1 Journal article-refereed

    Research areas

  • Anti-inflammatory activity, Antitumor screening, COX-1, COX-2, Docking studies, Dynamic simulations study, Naprosyn analogs, NCI cancer screening, Synthesis

ID: 16551590