Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3795-3803 |
| Number of pages | 9 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 50 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 9 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Sponge-derived fijianolide polyketide class : Further evaluation of their structural and cytotoxicity properties. / Johnson, Tyler A.; Tenney, Karen; Cichewicz, Robert H.; Morinaka, Brandon I.; White, Kimberly N.; Amagata, Taro; Subramanian, Balanehru; Media, Joseph; Mooberry, Susan L; Valeriote, Frederick A.; Crews, Phillip.
In: Journal of Medicinal Chemistry, Vol. 50, No. 16, 09.08.2007, p. 3795-3803.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=34548095481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548095481&partnerID=8YFLogxK
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 -