Antifungal sphingolipids for AIDS-related Mycoses
Principal Investigator: TADEUSZ MOLINSKI
Abstract: Russia has one of the highest rates of increase in new cases of AIDS in the developed world correlated with tumultuous social and economic upheaval in the past decade. The development of novel antifungal drugs with activity against AIDS-related opportunistic fungal disease, joined with regional efforts in drug discovery, is needed. Dimeric sphingolipids, which occur in marine sponges of restricted distribution, exhibit significant synergism in antifungal assays (in vitro) and may be useful leads in development of novel antimycotics with unique or complementary modes of action to clinical drugs. This AIDS-FIRCA proposal seeks to isolate and characterize novel dimeric sphingolipids from marine sponges of the family Leucettidae. New compounds will be isolated using solvent fractionation and chromatography and characterized using a variety of spectroscopic techniques, in particular mass spectrometry nuclear magnetic resonance spectroscopy (NMR) and circular dichroism (CD). Biological activity of pure antifungal compounds will be characterized using in vitro antifungal susceptibility testing in panel of fluconazole-resistant fungi. Lead compounds will be selected for advanced in vivo evaluation in murine models of fungemia.
Funding Period: 2003-04-01 - 2006-03-31
more information: NIH RePORT
- Rhizochalin A, a novel two-headed sphingolipid from the sponge Rhizochalina incrustataTatyana N Makarieva
Laboratory of the MaNaPro Chemistry, Pacific Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 690022 Vladivostok 22, Russia
J Nat Prod 68:255-7. 2005..Its structure has been established as the 2-ethyl carbamoate of rhizochalin on the basis of spectroscopic data and chemical transformations...
- Oceanalin A, a hybrid alpha,omega-bifunctionalized sphingoid tetrahydroisoquinoline beta-glycoside from the marine sponge Oceanapia spTatyana N Makarieva
Pacific Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Vladivostok
Org Lett 7:2897-900. 2005..The structure was elucidated using NMR and MS spectral analysis and chemical degradation. Oceanalin A exhibits in vitro antifungal activity against Candida glabrata with an MIC of 30 mug/mL...
- Rhizochalins C and D from the sponge Rhizochalina incrustata. A rare threo-sphingolipid and a facile method for determination of the carbonyl position in alpha,omega-bifunctionalized ketosphingolipidsTatyana N Makarieva
Laboratory of MaNaPro Chemistry, Pacific Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 690022, Vladivostok 22, Russian Federation
J Nat Prod 70:1991-8. 2007..Application of the latter method leads to a revision of the structure of oceanapiside and placement of the keto group at C-18 rather than C-11...