Synthesis and topoisomerase II inhibitory and cytotoxic activity of oxiranylmethoxy- and thiiranylmethoxy-chalcone derivatives.
In order to find potential anticancer drug candidate targeting topoisomerases enzyme, we have designed and synthesized oxiranylmethoxy- and thiiranylmethoxy-retrochalcone derivatives and evaluated their pharmacological activity including topoisomerases inhibitory and cytotoxic activity. Of the compounds prepared compound 25 showed comparable or better cytotoxic activity against cancer cell lines tested. Compound 25 inhibited MCF7 (IC(50): 0.49 ± 0.21 μM) and HCT15 (IC(50): 0.23 ± 0.02 μM) carcinoma cell growth more efficiently than references. In the topoisomerases inhibition test, all the compounds were inactive to topoisomerase I but moderate inhibitors to topoisomerase II enzyme. Especially, compound 25 inhibited topoisomerase II activity with comparable extent to etoposide at 100 μM concentrations. Correlation between cytotoxicity and topoisomerase II inhibitory activity implies that compound 25 can be a possible lead compound for anticancer drug impeding the topoisomerase II function.
College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk 712-702, Republic of Korea. yna7315@cu.ac.kr
Younghwa
Y
Na
Jung-Min
JM
Nam
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D000970:Antineoplastic Agents; D047188:Chalcones; D013440:Sulfides; D059005:Topoisomerase II Inhibitors; D002599:Chalcone; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II