Structurally diverse hamigerans from the New Zealand marine sponge Hamigera tarangaensis: NMR-directed isolation, structure elucidation and antifungal activity.
The NMR-directed investigation of the New Zealand marine sponge Hamigera tarangaensis has afforded ten new compounds of the hamigeran family, and a new 13-epi-verrucosane congener. Notably, hamigeran F (6) possesses an unusual carbon–carbon bond between C-12 and C-13, creating an unprecedented skeleton within this class. In particular, the structural features of 6, hamigeran H (10) and hamigeran J (12) imply a diterpenoid origin, which has allowed the putative biogenesis of three hamigeran carbon skeletons to be proposed based on geranyl geranyl pyrophosphate. All new hamigerans exhibited micromolar activity towards the HL-60 promyelocytic leukaemic cell line, and hamigeran G also selectively displayed antifungal activity in the budding yeast Saccharomyces cerevisiae. Homozygous deletion profiling (HOP) analysis suggests Golgi apparatus function as a potential target of this unusual class of sponge-derived terpenoids.
Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand. peter.northcote@vuw.ac.nz.
A Jonathan
AJ
Singh
Jonathan D
JD
Dattelbaum
Jessica J
JJ
Field
Zlatka
Z
Smart
Ethan F
EF
Woolly
Jacqueline M
JM
Barber
Rosemary
R
Heathcott
John H
JH
Miller
Peter T
PT
Northcote
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009520:New Zealand; D011161:Porifera / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004224:Diterpenes; D009285:Naphthoquinones