mycestericin-d and thermozymocidin

Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos++ +-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.

Topics: Acyltransferases; Alkylation; Animals; Ascomycota; Eicosanoic Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Immunosuppressive Agents; Interleukin-2; Mice; Propylene Glycols; Rats; Serine C-Palmitoyltransferase; Skin; Spleen

Mycestericins A, B, C, D and E were isolated from the culture broth of Mycelia sterilia ATCC 20349 along with thermozymocidin (= myriocin). Their structures were elucidated on the basis of spectroscopic studies and chemical evidence. The acetate of mycestericin C was identical with the acetate of 6,7-dihydromyriocin. Mycestericins suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction, with a potency similar to that of myriocin.

Topics: Animals; Antifungal Agents; Cell Division; Chromatography, High Pressure Liquid; Eicosanoic Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Immunosuppressive Agents; Lymphocyte Culture Test, Mixed; Lymphocytes; Magnetic Resonance Spectroscopy; Mice; Mitosporic Fungi; Stereoisomerism