Synthesis, Biological Evaluation and In Silico Studies of Some 2-Substituted Benzoxazole Derivatives as Potential Anticancer Agents to Breast Cancer

Kuzu B., Hepokur C., ALAGÖZ M. A., BURMAOĞLU S., ALGÜL Ö.

CHEMISTRYSELECT, vol.7, no.1, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 7 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1002/slct.202103559
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Keywords: anticancer activity, benzoxazole, COX inhibition, cytotoxic activity, molecular docking, CELL-CYCLE, ANTIOXIDANT STATUS, MOLECULAR DOCKING, THALIDOMIDE, INFLAMMATION, INHIBITORS, DRUG, CYCLOOXYGENASE-2, PROGRESSION, CELECOXIB
  • Ataturk University Affiliated: Yes


In an attempt to develop potent and selective anticancer agents, some 5- or 6- and N-substituted benzoxazol-2-carboxamide derivatives were designed, synthesized, and evaluated for their cyclooxygenase inhibitory, antioxidant, and anti-proliferative activity against MCF-7 and MDA-MB-231 cell lines. Among them 5-OMe, N-piperidine substituted (compound 30), 5-OMe, N-4-methylpiperidine substituted (compound 31) and 5-Cl, N-piperidine substituted (compound 34) benzoxazole 2-carboxamide compounds have a moderate inhibitory effect in COX-1 and COX-2 enzymes. Anti-proliferative studies show that compound 30 (IC50=5.35 mu M) and compound 31 (IC50=5.82 mu M) have similar activity to reference drug 5-FU (IC50=3.95 mu M) on MCF-7 cell but they have lower toxic effect for healthy WI-38 cell line. For the MCF-7 cell line, compounds 30 and 31 show approximately 1.5 times higher selectivity compared to the 5-FU control. Among the synthesized compounds 30, 31, and 34 had the best anti-proliferative effect and were used to perform flow cytometry and cell cycle analysis on MCF-7 cell line. To predict the binding modes and pharmacokinetic parameters of all compounds, in silico studies were carried out. These compounds may shed light on cancer treatment and cancer research.