Novel oxalamide derivatives for COXs expression and breast cancer: design, synthesis, biological evaluation, and docking studies


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Kuzu B., Hepokur C., Algul O.

Organic Communications, cilt.16, sa.3, ss.152-165, 2023 (ESCI) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 3
  • Basım Tarihi: 2023
  • Doi Numarası: 10.25135/acg.oc.154.2306.2820
  • Dergi Adı: Organic Communications
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier
  • Sayfa Sayıları: ss.152-165
  • Anahtar Kelimeler: antiproliferation, COXs expression, molecular docking, Oxalamides, western blotting
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

In the present study, new oxalamide-based compounds were designed from thalidomide and synthesized easily and with high yields (from 69% up to 93%) by a two-step method. The antiproliferative effects of synthesized 6a-d and 7a-d compounds on (ER+) MCF-7 and (ER-) MDA-MB-231 breast cancer cell line and human fibroblast WI-38 healthy cell line were investigated by the MTT method. The results showed that compound 7d was the most potent candidate against both MCF-7 and MDA-MB-231 cell lines with IC50 = 4.72 μM and 6.37 μM, respectively. To investigate whether antiproliferative effect of the compounds on breast cancer cell lines is dependent on COXs, expressions of COX-1/2 on the MCF-7 cell line were investigated by the Western-Blot technique. Among synthesized compounds, compound 7d increased the expression of both COX-1 and COX-2. The inhibition potential of compounds on COX-1/2 enzymes was investigated by molecular docking compared to inhibitor co-ligand celecoxib in crystal structures of COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1). Docking results indeed showed that compound 7d had a higher binding affinity for both COX-1 and COX-2 active sites. Consequently, the novel oxalamide-based compounds presented here may be important candidate molecules for the development of new COX-dependent antiproliferative agents.