title: Identification of dialkyl diacetylene diols with potent cancer chemopreventive activity.
abstract: An increasing importance of chemoprevention for controlling cancer risks prompted the discovery of new active cancer chemopreventive agents. In this study, we designed and synthesized substituted hexa-2,4-diyne-1,6-diols, more structurally simplified, tunable, and easily preparable than natural gymnasterkoreaynes, and evaluated their cancer chemopreventive activities by measuring concentration of doubling quinone reductase activity (CD), cell viability, and chemopreventive index (CI). Most of the diols exhibited good CD activity and low cytotoxicity. In particular, tetradeca-5,7-diyne-4,9-diol and 2-methyltetradeca-5,7-diyne-4,9-diol showed the best cancer chemopreventive activity, approximately equipotent to that of sulforaphane. And, by synthesizing optically active stereoisomers of selected active compounds, the effect of stereochemistry was also studied. Eventually, we produced a chemopreventive compound for in vivo study.
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, Republic of Korea.
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, 290 Daejeon-dong, Gangneung 210-340, Republic of Korea.
authors.forename: Ji Ho
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, 290 Daejeon-dong, Gangneung 210-340, Republic of Korea.
authors.forename: Kyungsu
authors.initials: K
authors.lastname: Kang
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, 290 Daejeon-dong, Gangneung 210-340, Republic of Korea.
authors.forename: Chu-Won
authors.initials: CW
authors.lastname: Nho
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, Republic of Korea. Electronic address: dyshin@gachon.ac.kr.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Shin
mesh_terms: D000114:Acetylene / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D016588:Anticarcinogenic Agents; D016660:NAD(P)H Dehydrogenase (Quinone); D000114:Acetylene
keywords: Cancer; Chemoprevention; Diyne; Quinone reductase; Stereoisomeric