Sponge-derived fijianolide polyketide class: further evaluation of their structural and cytotoxicity properties.
The sponge-derived polyketide macrolides fijianolides 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 fijianolides. In addition to fijianolides 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.
Johnson
Tyler A
TA
Department of Chemistry and Biochemistry and Institute for Marine Sciences, University of California, Santa Cruz, CA 95064, USA.
Tenney
Karen
K
Cichewicz
Robert H
RH
Morinaka
Brandon I
BI
White
Kimberly N
KN
Amagata
Taro
T
Subramanian
Balanehru
B
Media
Joseph
J
Mooberry
Susan L
SL
Valeriote
Frederick A
FA
Crews
Phillip
P
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D018942:Macrolides; D043823:Taxoids; C117306:isolaulimalide; C117305:laulimalide