title: Sponge-derived fijianolide polyketide class: further evaluation of their structural and cytotoxicity properties.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry and Institute for Marine Sciences, University of California, Santa Cruz, CA 95064, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Karen
authors.initials: K
authors.lastname: Tenney
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
authors.forename: Brandon I
authors.initials: BI
authors.lastname: Morinaka
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: White
authors.forename: Taro
authors.initials: T
authors.lastname: Amagata
authors.forename: Balanehru
authors.initials: B
authors.lastname: Subramanian
authors.forename: Joseph
authors.initials: J
authors.lastname: Media
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Valeriote
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D018942:Macrolides; D043823:Taxoids; C117306:isolaulimalide; C117305:laulimalide