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.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW006301-03
Application #
6897491
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Mcdermott, Jeanne
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
3
Fiscal Year
2005
Total Cost
$38,910
Indirect Cost
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Makarieva, Tatyana N; Dmitrenok, Pavel S; Zakharenko, Alexander M et al. (2007) 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 ketosphingolipids. J Nat Prod 70:1991-8
Makarieva, Tatyana N; Denisenko, Vladimir A; Dmitrenok, Pavel S et al. (2005) Oceanalin A, a hybrid alpha,omega-bifunctionalized sphingoid tetrahydroisoquinoline beta-glycoside from the marine sponge Oceanapia sp. Org Lett 7:2897-900
Makarieva, Tatyana N; Guzii, Alla G; Denisenko, Vladimir A et al. (2005) Rhizochalin A, a novel two-headed sphingolipid from the sponge Rhizochalina incrustata. J Nat Prod 68:255-7