Mimicry of annonaceous acetogenins: enantioselective synthesis of a (4R)-hydroxy analogue having potent antitumor activity.
The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2 were designed and synthesized structurally on the basis of the naturally occurring annonaceous acetogenin bullatacin, which was discovered as a typical member of the novel family of polyketides with potent cytotoxicity, antitumoral, and other biological activities. The preliminary screenings show that the IC(50) values of 2 were 1.6 x 10(-3) and 8 x 10(-2) microg/mL against HT-29 and HCT-8, respectively. A remarkable enhancement effect was observed by the activity comparison of 1c and its (4R)-hydroxylated analogue 2.
Jiang
Sheng
S
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, 354 Fenglin Road, Shanghai 200032, China.
Liu
Zhong-Hai
ZH
Sheng
Gang
G
Zeng
Bu-Bing
BB
Cheng
Xiao-Guang
XG
Wu
Yu-Lin
YL
Yao
Zhu-Jun
ZJ
D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D003110:Colonic Neoplasms; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007422:Intestines; D018716:Molecular Mimicry; D015394:Molecular Structure; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
C466878:3-((2R,13S)-2,13-dihydroxy-14-(2-(2S)-hydroxydodecyloxy)ethoxy)tetradecyl-5-methyl-5H-furan-2-one; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; C061022:bullatacin; D004317:Doxorubicin