title: Antimicrobial activities of indolocarbazole and bis-indole protein kinase C inhibitors. II. Substitution on maleimide nitrogen with functional groups bearing a labile hydrogen.
abstract: New compounds, structurally related to the potent protein kinase C inhibitor staurosporine, and substituted on the imide nitrogen with a functional group bearing a labile hydrogen (hydroxymethyl, amino, hydroxy), were synthesized. Their in vitro inhibitory potencies towards protein kinase C and protein kinase A showed that N-hydroxymethyl and N-hydroxy substitution, unlike alkyl substitution, can provide efficient protein kinase C inhibitors. The antimicrobial activities of these new compounds against Streptomyces chartreusis and Streptomyces griseus, Bacillus cereus, Escherichia coli, Candida albicans and Botrytis cinerea were examined. They proved to be inactive against E. coli and two fungi. The results suggest that there is no link between in vitro inhibition of protein kinase C and inhibition of growth and sporulation of the two Streptomyces tested. Unlike indolocarbazole maleimides, bis-indole maleimides are active against the two Streptomyces species.
authors.affiliation: Université Blaise Pascal, Laboratoire de Chimie Organique Biologique, Aubière, France.
authors.forename: E R
authors.initials: ER
authors.lastname: Pereira
authors.forename: S
authors.initials: S
authors.lastname: Fabre
authors.forename: M
authors.initials: M
authors.lastname: Sancelme
authors.forename: M
authors.initials: M
authors.lastname: Prudhomme
authors.forename: M
authors.initials: M
authors.lastname: Rapp
mesh_terms: D002227:Carbazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002227:Carbazoles; D007211:Indoles; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C