title: Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol analogue with increased antiproliferation activity and cell selectivity.
abstract: Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol-inspired antiproliferative agents.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou 730000 (China), Fax: (+86) 931-8915557.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Kang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yan
authors.forename: Ting-Wen
authors.initials: TW
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Dai
authors.forename: Xiu-Zhuang
authors.initials: XZ
authors.lastname: Li
authors.forename: Xia-Zhen
authors.initials: XZ
authors.lastname: Bao
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Du
authors.forename: Cui-Hong
authors.initials: CH
authors.lastname: Yuan
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Ren
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Jin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002338:Carotenoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C534790:3,3'-dihydroxyisorenieratene; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D002338:Carotenoids; C010118:4,4'-dihydroxystilbene; D000077185:Resveratrol
keywords: antiproliferation; cell cycle; isoprene units; methylation reactions; resveratrol