Bioactive metabolites from halophilic fungi
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
Fungi are prolific sources of structurally novel and biologically active compounds. Over the past decades terrestrial fungi have been a major source of bioactive metabolites but little attention was paid to other habitats. Recently, increasing attention has been devoted to marine fungi as they too are a potential source of compounds for the development of new pharmaceutical agents. In searching for bioactive metabolites from marine fungi, several extracts showed significant activity against the P388 murine leukaemia cell line. These strains were grown in different culture conditions to optimise bioactivity and the optimal conditions were chosen for scale up. Bioassay- and/or ¹H NMR-guided separation of active extracts led to the isolation of twenty two compounds. The structures of these compounds were elucidated using spectral analysis techniques especially mass spectrometry and NMR spectroscopy (¹H and ¹³C NMR, COSY, NOESY, HSQC and CIGAR). From a Chaetomium sp. (A34) the known compound chetomin was isolated. It exhibited very potent P388 activity with IC₅₀ 11.2 ng/mL. From an isolate of Chaetomium globosum (N60), three new cytochalasins named chaetoglobosins Q, R and S were isolated, together with nine previously characterised compounds: chaetoglobosins A, B, D and J; prochaetoglobosins I and II; chaetoviridins A and B, and ergosterol peroxide. In the assay against the P388 murine leukaemia cell line, most of these compounds exhibited significant activity (IC₅₀ 1943-3988 ng/mL). In addition, some compounds also showed antimicrobial activities. Examination of an isolate of Phoma resulted m the isolation of two simple compounds: 2,5-dihydroxybenzoic acid and 2,5-dihydroxybenzyl alcohol. The former was inactive while the latter showed significant P388 activity (IC₅₀ 3660 ng/mL). Three compounds, identified as bikaverin, beauvericin and bassiatin, were isolated from the filtrate of Fusarium sp. (A l 45). In the P388 assay, these compounds exhibited strong, moderate and no activity respectively (IC₅₀ 304, 4126 and > 12500 ng/mL, respectively). An isolate of Aspergillus fumigatus (A 151) was investigated for bioactive compounds. ·Culture broths incubated for different periods produced different metabolites. From the mycelium of a broth cultured for eleven weeks, one biologically active compound, xanthocillin-X dimethyl ether (IC50 606 ng/mL for the P388 cell line), was obtained. From the filtrate of a four week culture, two known compounds, 12𝛼-fumitremorgin C and fumagillin, and a novel compound, fumagiringillin, were isolated.