DNA topoisomerases are complex unique enzymes which alter the topological state of DNA and play important role in DNA replication, transcription, recombination and chromosomal segregation. Topoisomerases have been reported as cidal target of many therapeutic agents including antibacterial (quinolones) and antineoplastic agents (camptothecin, etoposide etc.). We have evaluated the inhibitory effect of a series of novel glycosyl amino acid derivatives (synthesized in CDRI on a targetbased synthesis against Topo-I) in a number of pathogenic fungi following NCCLS guidelines. Most of the derivatives showed a significant activity (MICs 3.12-25 ug/ml) against Candida albicans, a common nosocomial infection in immunocompromised patients. Further, the potential derivatives were tested in target-based assay for Topo-I using cell-free extracts of C. albicans which showed 60-70% inhibition (relaxation of supercoiled plasmid pBR322). Camptothecin, used as standard Topo-I inhibitor, exhibited 64% inhibition. A good correlation (r2 = 0.902) was obtained between in vitro MICs of glycosyl amino acid derivatives and their subsequent inhibitory effect on Topo-I catalysis. Further validation is warranted to confirm the antifungal activity of these derivatives.
Full conference title:
13th Annual Focus on Fungal Infections
- FFI 13th (2003)