Browsing by Author "Singh, Ameet Jonathan"

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Secondary metabolites from the New Zealand marine sponge Mycale hentscheli
(Te Herenga Waka—Victoria University of Wellington, 2007) Singh, Ameet Jonathan
The New Zealand marine sponge Mycale hentscheli is the source of three classes of biologically active secondary metabolites, each with a different activity profile. Mycalamides A, B and D (102-104) inhibit the elongation stage of protein synthesis, where 102 and 103 have also been shown to reverse the morphology of ras-transformed T-cells to normal. The dilactone macrolide pateamine (105) is also a protein synthesis inhibitor, but at the initiation stage of translation. The polyoxygenatcd macrolide peloruside A (106) has been shown to cause cells to accumulate in the G2-M phase of mitosis by promoting microtubule polymerisation much like the highly successful antitumor drug paclitaxel (Taxol) (1) and thus has become a promising pharmaceutical candidate and a popular synthetic target. A study of a wild sample of M. hentscheli collected from Kapiti Island initiated by West and continued in this study resulted in the isolation of 104, 106 and also revealed a new compound, peloruside B (141). Large-scale extractions of wild and aquacultured Pelorus Sound specimens of M. hentscheli using a combination of normal- and reversed-phase chromatographic methods and standard spectroscopic techniques resulted in the isolation of 102, 106 and three new compounds, mycalamide E (107). and pelorusides C-D (142-143). Mycalamide E (107), the 6-des-O-methyl analogue of mycalamide A (102) was found to be 30 times less cytotoxic than 102 across four cell lines. Peloruside B (141), the 3-des-O-methyl analogue of peloruside A (106) was found to be approximately three times less cytotoxic than 106, yet still arrested cells at the G2-M phase of mitosis. Peloruside C (142), identified as the 3,7-des-0-methyl-8,9-didehydroxy-8-ene analogue of peloruside A (106), was found to be cytotoxic at nanomolar concentrations 15 times less than 106 but showed no antimitotic activity. Peloruside D (143), containing the 16-membered macrolide ring but with an unusual cyclisation about the C-7 to C-l I region and deoxygenation at the C-8 position, was found to be inactive at micromolor concentrations against the HL-60 cell line.
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The Structure-Directed Isolation of New Secondary Metabolites from South Pacific Marine Sponges
(Te Herenga Waka—Victoria University of Wellington, 2012) Singh, Ameet Jonathan; Northcote, Peter
This study describes the NMR-directed isolation and structure elucidation of nine new and several known compounds from New Zealand and Tongan marine sponges. An examination of the New Zealand marine sponge Hamigera tarangaensis resulted in the isolation of five new congeners of the hamigeran family (60, 62, 64–66) and a new 13-epi-neoverrucosane (67). The nature of the new hamigeran congeners in particular has allowed a diterpenoid biogenesis to be proposed that has been missing from the chemical literature. Of these compounds, hamigeran F (60) possesses an unusual fourth carbocycle which forms a cage-like structure, hamigeran H (64) is the only congener that retains its full complement of isoprenyl carbons, and hamigeran J (66) is a regioisomer of hamigeran A (52). An improvement on NMR-based screening using the HMBC experiment is discussed. Semi-purified extracts from New Zealand and Tongan sponges were screened in this manner. From this, the known compounds plakinidines A and B were isolated from a collection of the Tongan sponge Plakortis quasiamphiaster. The isolation of guaiazulene (143) from an unidentified Tongan sponge is believed to be the first instance of its occurence from an organism of this kind. Examination of an undescribed Tongan marine sponge produced a new polyketide-derived γ-lactone (144). A spectroscopic investigation into the Tongan marine sponge Cacospongia mycofijiensis afforded several known, yet biologically interesting secondary metabolites. Among these, the re-isolation of zampanolide (194) resulted in the discovery of its microtubule-stabilising activity. Attempts to procure additional quantities of 194 also yielded two new latrunculin congeners (196 and 197). These two compounds feature substitution of a hydroxyl group at C-18 in place of the typical methine proton. A diastereomeric relationship is proposed for these compounds. Using the HMBC spectra of 66 sponges from New Zealand and Tonga, a rudimentary analysis was undertaken in an attempt into compare the secondary metabolite profile of temperate and subtropical sponges. The results show a definite bias towards Tongan sponges with respect to the amount of secondary metabolites they contain, but no discernible favour towards either location in regards to the diversity of their correlation data.