Burak Kuzu1,2, Ceylan Hepokur3, Burcin Turkmenoglu4, Serdar Burmaoglu5, Oztekin Algul1,6. 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mersin University, Mersin, 33169, Turkey. 2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, 65080, Turkey. 3. Department of Basic Pharmaceutical Sciences, Division of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, 58100, Turkey. 4. Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, Erzincan, 24100, Turkey. 5. Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240, Turkey. 6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erzincan Binali Yildirim University, Erzincan, 24100, Turkey.
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.
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.