DNA binding compounds targeting fungal pathogens: an emerging concept in the discovery of novel antifungal agents.
With the urgent need for novel agents to combat emerging fungal resistance to existing drugs, activity in the exploration of small molecule DNA binders has increased. Recently, selected cationic heterocyclic compounds belonging to a broad class of molecules known to bind to the minor groove of DNA were revealed to have potent antifungal activity. These molecules are different from the conventional DNA-interacting drugs such as topoisomerase inhibitors, DNA alkylators or intercalators. Selected compounds are fungicidal towards a variety of pathogenic yeasts and molds, and a selected lead compound is efficacious in a mouse model of systemic candidosis.
Lou
Lillian
L
Genelabs Technologies Inc., Redwood City, CA 94063, USA. LillianL@genelabs.com
Velligan
Mark
M
Roberts
Christopher
C
Stevens
David A
DA
Clemons
Karl V
KV
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism*; D025141:Drug Resistance, Fungal; D006801:Humans; D051379:Mice; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D059005:Topoisomerase II Inhibitors
D000935:Antifungal Agents; D059005:Topoisomerase II Inhibitors; D004247:DNA