Design, synthesis and in vitro antiproliferation activity of some 2-aryl and -heteroaryl benzoxazole derivatives


Kuzu B., ÖZSOY C., TÜRKMENOĞLU B., BURMAOĞLU S., ALGÜL Ö.

FUTURE MEDICINAL CHEMISTRY, vol.14, pp.1027-1048, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14
  • Publication Date: 2022
  • Doi Number: 10.4155/fmc-2022-0076
  • Journal Name: FUTURE MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded, Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.1027-1048
  • Keywords: apoptosis, benzoxazole, cell-cycle, cytotoxicity, flow cytometry, molecular docking, phortress, 2-SUBSTITUTED BENZOXAZOLES, ANTICANCER EVALUATION, FACILE PREPARATION, BENZOTHIAZOLES, PHORTRESS, EFFICIENT, CATALYST, DRUG, 2-ARYLBENZOXAZOLE, AGENTS

Abstract

Background: Phortress produces reactive electrophilic metabolites that form DNA adducts only in sensitive tumor cells. The authors converted the 2-phenylbenzothiazole nucleus in phortress to 2-aryl and -heteroaryl benzoxazole derivatives (11 new and 14 resynthesized). All synthesized compounds were studied for antitumor activity in various cancer cells. Materials & methods: Cytotoxicity, cell morphology, flow cytometry and cell-cycle analyses of compounds were performed and more active derivatives were tested in the MCF-7 cell line. Conclusion: Methyl 2-(thiophen-2-yl)benzo[d]oxazole-6-carboxylate (BK89) has a higher effect than fluorouracil to induce apoptotic cell death (apoptosis value of 49.44%). Cell-cycle analysis shows that the compounds BK89 and methyl 2-(furan-2-yl)benzo[d]oxazole-6-carboxylate (BK82) can be used as potential cell-cycle blockers by arresting MCF-7 cells in G0/G1 phase at rates of 63% and 85%, respectively.