Michel Dherbomez

Synthesis and antifungal activity of oxygenated cholesterol derivatives

A series of oxygenated cholesterol derivatives were prepared from new synthetic methods and evaluated for their in vitro antimicrobial properties against human pathogens. The activity was highly dependent on the structure of the different compounds involved. The best results were obtained with hydroxy ketones 2, 4 and 5 and diketone 7 exhibiting activities against S. cerevisiae (ATCC 28383) and Candida albicans (CIP 1663-86). For example, compound 2 exhibited high activities against C. albicans (CIP 1663-86) and Amphotericine B and miconazole resistant strain C. albicans (CIP 1180-79) at a concentration of 1.5 microg/mL.

Stereoselective Synthesis of 7α‐ and 7β‐Aminocholesterol as Δ8‐Δ7 Sterol Isomerase Inhibitors, with Fungicidal Activities towards Resistant Strains

A mixture of epimeric 7α- and 7β-aminocholesterol was shown to be a stronger inhibitor of yeast cell growth than morpholine inhibitors. In fact, this epimeric mixture inhibits Δ8-Δ7-sterol reductase. This epimeric mixture is fungicidal and active against Saccharomyces cerevisiae resistant strains. Therefore, 7α- and 7β-aminocholesterol were selectively synthesized. According to in vitro bioassay studies on resistant strains such as Candida tropicalis [Amphotericin B resistant; minimum inhibitory concentration (MIC) of Amp B: 12.5 μg/mL], the MIC values for 7β-aminocholesterol and 7α-aminocholesterol were found to be 0.8 μg/mL and 1.5 μg/mL, respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002)

Synthesis of 6(α,β)-aminocholestanols as ergosterol biosynthesis inhibitors

Abstract Δ 7 -5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover Δ 5 -unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6β-aminocholestanol is a potent antifungal agent.

Stereoselective synthesis of 7α- and 7β-aminocholestanol as potent fungicidal drugs

Potentially lymphotropic 7α- and 7β-aminocholestanol were stereoselectively synthesized. In vitro bioassay studies have shown that these fungicidal lipidic derivatives possess strong antifungal activity against Candida spp resistant strains to amphotericin B, 5-fluorocytosine and azoles.

Synthesis of 25-aminosterols, new antifungal agents.

25-aminolanostenol 1 and 25-aminocholesterol 2 were hemisynthesized from natural sterols and tested in vitro against Candida albicans. The biological activity of compound 1 was rather weak, whereas 2 exhibited in vitro antifungal activity with MIC value of 4 microM.