title: Chromenylchalcones showing cytotoxicity on human colon cancer cell lines and in silico docking with aurora kinases.
abstract: Due to toxicity problems, various plant-derived compounds have been screened to find the chemotherapeutic agents. As anticancer therapeutic agents, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. Chromenones show anticancer activities too. Therefore, hybrids of chalcone and chromenone may be potent chemotherapeutic agents. We prepared 16 synthetic chromenylchalcones and applied a clonogenic long-term survival assay method for them on HCT116 human colorectal cancer cell lines. One of chromenylchalcones tested here, chromenylchalcone 11, showed IC50 of 93.1nM which can be competed with the IC50 values of well-known flavonoids such as catechin gallate and epicatechin gallate. Further biological experiments including cell cycle analysis, apoptosis assay, Western blot analysis, and immunofluorescent microscopy were carried out for this compound. In addition, in vitro kinases binding assay performed to explain its molecular mechanism demonstrated the compound inhibited aurora kinases. The binding modes between chromenylchalcone 11 and aurora kinases were elucidated using in silico docking experiments. These findings could be used for designing cancer therapeutic or preventive plant-derived chromenylchalcone agents.
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Hyuk
authors.initials: H
authors.lastname: Yoon
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Ahn
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D064127:Aurora Kinases / Q000737:chemistry* / Q000378:metabolism; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D015153:Blotting, Western; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding
chemical_list: C585736:1-(6-methoxy-2H-chromen-3-yl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one; D000970:Antineoplastic Agents; D001578:Benzopyrans; D047188:Chalcones; D002392:Catechin; D064127:Aurora Kinases