2. Academic Validation
  3. Structural alterations based on naproxen scaffold: Synthesis, evaluation of antitumor activity and COX-2 inhibition, and molecular docking

Structural alterations based on naproxen scaffold: Synthesis, evaluation of antitumor activity and COX-2 inhibition, and molecular docking

  • Eur J Med Chem. 2018 Oct 5:158:134-143. doi: 10.1016/j.ejmech.2018.09.007.
Walaa M El-Husseiny 1,  Magda A-A El-Sayed 2,  Naglaa I Abdel-Aziz 3,  Adel S El-Azab 4,  Yousif A Asiri 5,  Alaa A-M Abdel-Aziz 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
  • 2 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
  • 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt.
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt.
  • 5 Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
  • 6 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. Electronic address: almoenes@ksu.edu.sa.
PMID: 30216848 DOI: 10.1016/j.ejmech.2018.09.007
Abstract

A new series of non-carboxylic naproxen analogues, bearing a variety of ring systems, such as oxadiazoles 3a-c and 6a-c, cycloalkanes 4a-d, cyclic imides 5a-c, and triazoles 7-9 and 10a-c, was synthesized. In addition, in vitro antitumor activity and cyclooxygenase isozymes (COX-1/COX-2) inhibition assay of the target compounds 3-10 was studied. The results of the antitumor activity assays indicated that compounds 4b, 6c, 10b, and 10c exhibited the greatest antitumor activities against the tested cell lines MCF-7, MDA-231, HeLa, and HCT-116, with an IC50 range of 4.83-14.49 μM. By comparison, the reference drugs doxorubicin, afatinib, and celecoxib yielded IC50 values of 3.18-26.79, 6.20-11.40, and 22.79-42.74 μM, respectively. Furthermore, in vitro COX-1/COX-2 inhibition testing showed that the compounds 4b, 6c, 10b, and 10c exhibited effective COX-2 inhibition, with IC50 values of 0.40-1.20 μM, and selectivity index (SI) values of >62.50-20.83, using celecoxib as a reference drug (IC50 = 0.11 μM; COX-2 SI: >227.20). Compounds 6c and 10c, which were potent COX-2 inhibitors, were docked into the COX-2 binding site, where these compounds exhibited strong interactions.

Keywords

Antitumor activity; COX-1/COX-2 inhibition assay; Docking study; Naproxen scaffold; Synthesis.

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