Sensitive assay for antifungal activity of glucan synthase inhibitors that uses germ tube formation in Candida albicans as an end point.
We implemented a simple, sensitive, objective, and rapid cellular assay to reveal the antifungal activity of a novel class of glucan synthase inhibitors. The assay, especially useful for early drug discovery, measures the transformation of Candida albicans from the yeast form to the hyphal form. Test compounds were ranked by potency (50% inhibitory concentration) and efficacy (percent inhibition of germ tube formation); the intra-assay coefficients of variation for these parameters were 17 and 5%, respectively. The germ tube formation assay proved useful for the early-stage antifungal characterization of a novel class of glucan synthase inhibitors discovered at Pharmacia. Drug concentrations required in this assay to inhibit germ tube formation were lower for 90% of the novel compounds than the concentrations required to determine MICs. The method may have utility for other mechanistic classes of antifungal compounds during the hit-to-lead transition of drug discovery.
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005964:Glucosyltransferases; C040232:glucan synthase