annual reports in medicinal chemistry—38 issn: 0065-7743

Peptides and Polymers - A cyclic peptide SF-2822 (4) showed in vitro activity against C. albicans (10). Other reported cyclic peptides and cilofungin were shown to have in vitro antifungal activity (11). New peptides obtained from the MUCD1 domain of the saliva mucin glycoprotein MUC7 were obtained from the C-terminus of the MÜC7D1 protein and range in size from 8 to 20 amino acids in length, having a net positive charge (12). An antifungal family of DNA-binding cationic polyheterocyclic molecules showing fungicidal activity against Candida spp. was reported. The initial lead, GL-047296, has fungicidal activity against Candida spp. A metabolically improved derivative, GL-663142, was reported to be active against Candida spp., some Aspergillus spp. and C. neoformans subtypes. It was fungicidal against Fusarium, dermatophytes, and certain endemic dimorphic species, with most MIC and MFC values <10 ng/mL. The agent was active against C. albicans strains resistant to fluconazole and fluocytosine. The derivative GL-406349, displayed efficacy in murine systemic candidosis models (5 mg/kg) with a half-life of 166 minutes (13). C. albicans presents ß-1,2- oligomannosides on the cell surface, and in a recent report, synthetic analogs of these oligomannosides prevent intestinal colonization (14).

Purines - Recently, a series of purine derivatives (5) with antifungal properties has been disclosed indicating the compounds act by inhibiting the C. albicans protein kinase CIV1. A representative compound inhibited in vitro purified CIV1 enzyme with an IC5o value of 5.6 nM and exhibited an MIC value against C. albicans of 12.5 ng/mL (15).

Miscellaneous - A number of compounds exhibiting a variety of mechanisms have been described. Hydrazone (6), and related hydrazides and thiosemicarbazones showed in vitro MIC activity against C. albicans (< 1 ng/mL); natural product isolates showing antifungal activity from a Serpula himantoides strain gave succinimides and maleimides, for example himanimide A (7) (16,17). Sordarins and sordaricins selectively inhibit fungal protein synthesis by interfering with the translational complex containing co-factor Elongation Factor 2 (EF-2). Two new azasordarin derivatives GW-471552 (8), and GW-471558 (9), were shown to be active against C. albicans with an MIC < l^g/mL and recently studied in vivo against Pneumocystis carinii in Immunosuppressed-rat models (18,19). A new sodaricin derivative (10), was reported with potent in vitro MIC against C. albicans (< 0.06 ng/mL) and C. glabrata (0.125 ng/mL) (20,21). Benzofuran (RO-09-4609, H) was initially reported as an N-myristoyltransferase inhibitor with the finding that these compounds are

Was this article helpful?

0 0

Post a comment