TY - JOUR
T1 - Sponge-derived fijianolide polyketide class
T2 - Further evaluation of their structural and cytotoxicity properties
AU - Johnson, Tyler A.
AU - Tenney, Karen
AU - Cichewicz, Robert H.
AU - Morinaka, Brandon I.
AU - White, Kimberly N.
AU - Amagata, Taro
AU - Subramanian, Balanehru
AU - Media, Joseph
AU - Mooberry, Susan L.
AU - Valeriote, Frederick A.
AU - Crews, Phillip
PY - 2007/8/9
Y1 - 2007/8/9
N2 - The sponge-derived polyketide macrolides frjianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a future study of the biosynthetic pathway that produces the frjianolides. In addition to frjianolides A and B, six new fijianolides, D-I (7-12), were isolated, each with modifications to the C-20 side chain of the macrolide ring. Compounds 7-12 exhibited a range of in vitro activities against HCT-116 and MDA-MB-435 cell lines. Fijianolides 8 and 10 were shown to disrupt interphase and mitotic division, but were less potent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency mice demonstrated significant inhibition of growth in HCT-116 tumors over 28 days.
AB - The sponge-derived polyketide macrolides frjianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a future study of the biosynthetic pathway that produces the frjianolides. In addition to frjianolides A and B, six new fijianolides, D-I (7-12), were isolated, each with modifications to the C-20 side chain of the macrolide ring. Compounds 7-12 exhibited a range of in vitro activities against HCT-116 and MDA-MB-435 cell lines. Fijianolides 8 and 10 were shown to disrupt interphase and mitotic division, but were less potent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency mice demonstrated significant inhibition of growth in HCT-116 tumors over 28 days.
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U2 - 10.1021/jm070410z
DO - 10.1021/jm070410z
M3 - Article
C2 - 17622130
AN - SCOPUS:34548095481
VL - 50
SP - 3795
EP - 3803
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 16
ER -