Amino acid conjugated sophorolipids: A new family of biologically active functionalized glycolipids

Sophorolipids ( SLs) are extra cellular glycolipids produced by Candida bombicola ATCC 22214 when grown in the presence of glucose and fatty acids. These compounds have a disaccharide head group connected to a longchain hydroxyl- fatty acid by a glycosidic bond. To explore structure- activity of modified SLs, a new family of amino acid- SL derivatives was prepared. Synthesized analogs consist of amino acids linked by amide bonds formed between their alpha- amino moiety and the carboxyl group of ring-opened SL fatty acids. Their preparation involved the following: ( i) hydrolysis of a natural SL mixture with aqueous alkali to give SL free acids, ( ii) coupling of free acids to protected amino acids using dicarbodiimide, and ( iii) removing amino acid carboxyl protecting groups. These conjugates were evaluated for their antibacterial, anti-HIV, and spermicidal activity. All tested analogs showed antibacterial activity against both gram + ve and gram - ve organisms. Leucine- conjugated SL was most efficient. For example, the minimum inhibitory concentrations ( MIC) for Moraxella sp. and E. coli were 0.83 and 1.67 mg/ mL, respectively. Among the alkyl esters of amino acid conjugated SLs, the ethyl ester of leucine-SLs was most active. Against Moraxella sp., S. sanguinis, and M. imperiale, MIC values are 7.62 x 10(-4), 2.28 x 10(-3) and 1.67 mg/ mL, respectively. All compounds displayed virus-inactivating activity with 50% effective concentrations (EC50) below 200 Ag/ mL. The EC50 of leucine- SL ethyl ester was 24.1 Ag/ mL, showing that it is more potent than commercial spermicide nonoxynol- 9 ( EC50 approximate to 65 mu g/ mL).