97(P42) スフィンゴシン様脂質部分をもつ新規抗真菌抗生物質TKR1785の構造と生物活性(ポスター発表の部)

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Recently there are many reports showing involvement of the sphingolipid metabolism pathway in apoptosis and various cellular signal transduction systems. In the course of our screening for antifungal antibiotics, we discovered antifungal antibiotics named TKR1785-I and -II, from a cultured broth of Penicillium sp. TKR1785. The compounds were purified by EtOAc extraction and ODS HPLC. Their structures were determined on the basis of spectral analyses including 2D NMR (HSQC, ^1H-^1H COSY, HOHAHA, HMBC). TKR1785-I had a structure composed of a sphingosine-like lipid moiety (C_<19>H_<38>NO_3), L-valine, and serinol. TKR1785-II had a structure composed of the lipid, isoleucine and serinol. TKR1785-I and -II had antifungal activity against various fungi including Candida sp., Aspergillus fumigatus, Cryptococcus neoformans. Sphingosine-like lipid moiety (1) had antifungal activity against Aspergillus fumigatus and Cryptococcus neoformans. TKR1785-I and 1 induced apoptosis of HL-60 human myelocytic leukemia cells and had inhibitory activities of mixed lymphocyte reaction. Also, TKR1785-I had growth inhibitory activitiy of human tumor cell lines. The sphingosine-like lipid moiety of TKR1785 will be important for its variety of biological activities, which may be caused through an effect on the sphingolipid biosynthesis.
1999-09-01