title: Synthesis and topoisomerases inhibitory activity of heteroaromatic chalcones.
abstract: The critical role of nuclear topoisomerase enzymes during cell proliferation process guided topoisomerases to be one of the major targets for anticancer drug development. We have designed and synthesized 22 heteroaromatic ring incorporated chalcone derivatives substituted with epoxide or thioepoxide. Topoisomerase enzyme inhibitory activity and cytotoxic tests were also conducted to evaluate compounds' pharmacological efficacy. In the topoisomerase I inhibitory test, compound 1 was most active one, 24% of inhibition at 20μM, among all the compounds but it was lower than camptothecin. Compounds 9, 11, and 13 inhibited the function of topoisomerase II more strongly than etoposide with almost same magnitude (around 90% and 30% inhibition at 100 and 20μM, respectively) which were higher than those of etoposide (72% and 18% inhibition). In the cytotoxicity test, compound 9 inhibited T47D cancer cell growth with the IC50value of 6.61±0.21μM. On the other hand, compound 13 (IC50: 4.32±0.18μM) effectively suppressed MDA-MB468 cancer cell growth.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Han-Bit
authors.initials: HB
authors.lastname: Yu
authors.affiliation: College of Pharmacy, CHA University, Pocheon 487-010, Republic of Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Kwak
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, CHA University, Pocheon 487-010, Republic of Korea. Electronic address: yna7315@cha.ac.kr.
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026942:DNA Topoisomerases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D059003:Topoisomerase Inhibitors; D026942:DNA Topoisomerases
keywords: Anticancer activity; Heteroaromatic chalcones; Topoisomerases inhibitors