Antifungal Activity of C-27 Steroidal Saponins

Abstract

As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study.

In vitro activity and in vivo efficacy of the saponin diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside hydrochloride (HSM1) alone and in combination with daptomycin and vancomycin against Gram-positive cocci

“…Saponins form complexes with sterols and cause sterol-dependent membrane permeabilization. The antimicrobial activity of saponins is generally attributed to these membranepermeabilizing properties (Datta et al, 2009;Yang et al, 2006). Studies have demonstrated that membrane impermeability plays an important role in resistance to antibiotics.…”

“…They have also been associated with a variety of effects on human health, such as lowering cholesterol, enhancing immune responses as cancer chemotherapy agents and protecting against acute hepatic failure, and pathogenic fungi and other micro-organisms (Qiang et al, 2010;Yang et al, 2006;Ying-Wan et al, 2010). …”

“…The search for alternative therapeutics is growing and, in particular, it is becoming critical to identify effective agents to treat multidrug-resistant Grampositive infections with novel mechanisms of activity. Saponins were originally classified as any of various plant glycosides and marine organisms that form soapy lathers when mixed and agitated with water, and thus have been used routinely as detergents, foaming agents and emulsifiers (Saleem et al, 2010;Yang et al, 2006). These natural surfactants were later found to be mainly glycosides of steroids and triterpenes, which exist widely in terrestrial plants, including many significant foods, forage crops and herbal medicinal plants (Qi et al, 2006;Simons et al, 2006).…”

“…It is believed that these saponins can form complexes with sterols of the erythrocyte membrane, thus causing an increase in permeability and the subsequent loss of haemoglobin. However, the detailed mechanism of action of this haemolytic cascade remains unclear (Myszka et al, 2003;Yang et al, 2006). Diosgenyl 2-amino-2-deoxyb-D-glucopyranoside hydrochloride (HSM1) is an unnatural saponin.…”

Synthesis, Antifungal Activity, and Structure−Activity Relationships of Coruscanone A Analogues

“…3 As outlined in Scheme 1, the synthetic sequence starts with Wittig condensation between a maleic anhydride derivative, e.g., 2-methylmaleic anhydride (2), 2,3-dimethylmaleic anhydride (3) or 2-phenylmaleic anhydride (4) and a phosphorane (16-21, refer to Experimental section for their structures) prepared from the corresponding α-methyl ketone in a three step sequence, via brominated α-methyl ketone (5-9) and phosponium salt (10-15). The key step is the base-catalyzed rearrangement of the resulting 4-ylidenebutenolide (22)(23)(24)(25)(26)(27)(28)(29), affording the corresponding cyclopent-4-ene-1,3-dione (30-37). Alkylation or acylation of the cyclopentenediones yields the enolic hydroxy substituted product (38-52).…”