3-Nitrocoumarin is an efficient inhibitor of budding yeast phospholipase-C.
3-Nitrocoumarin is described in the literature as a specific inhibitor of mammalian phospholipase-C and here we studied the effect of 3-nitrocoumarin on budding yeast phosphatidylinositol-specific phospholipase-C and its effect on yeast growth. 3-Nitrocoumarin is a powerful inhibitor in vitro of the yeast Plc1 protein with an IC(50) of 57 nM and it is also an inhibitor of yeast growth in minimal media at comparable concentrations. Moreover at the same concentration it inhibits the glucose-induced PI-turnover. Since the effects of 3-nitrocoumarin on yeast growth are superimposable on the growth phenotype caused by PLC1 gene deletion we can conclude that 3-nitrocoumarin is a specific and selective inhibitor of yeast phospholipase-C. In addition we show that 3-nitrocoumarin was also an effective inhibitor of the pathogenic yeast Candida albicans.
Tisi
R
R
Dipartimento di Biotecnologie e Bioscienze, Università di Milano, Bicocca Piazza delle Scienze 2, 20126-Milano, Italy.
Coccetti
P
P
Banfi
S
S
Martegani
E
E
D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009574:Nitro Compounds / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
C446262:3-nitrocoumarin; D003374:Coumarins; D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D010738:Type C Phospholipases; C432456:phospholipase C1; D005947:Glucose