Antimicrobial Activities of Indolocarbazole and Bis-indole Protein Kinase C Inhibitors. II. Substitution on Maleimide Nitrogen with Functional Groups Bearing a Labile Hydrogen.

Abstract

Newcompounds, 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 TV-hydroxymethyl and N-hydroxy substitution, unlike alkyl substitution, can provide efficient protein kinase C inhibitors. The antimicrobial activities of these new compoundsagainst 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.

Pityriarubins, Novel Highly Selective Inhibitors of Respiratory Burst from Cultures of the Yeast Malassezia furfur: Comparison with the Bisindolylmaleimide Arcyriarubin A

“…22, 23, 37–39 Furthermore, substitution of the imido hydrogen by methyl, hydroxyl or hydroxymethyl residues resulted in partial to total loss of PKC inhibitory activity 17. 18, 22 Surprisingly, substitution of the maleimide moiety by the spirane structure provides highly specific and potent inhibitors with low cellular toxicity. None of the previously reported analogues of arcyriarubin A presented a selectivity comparable to that of the pityriarubins, thus it is reasonable, especially from a spatial point of view, to postulate a still unknown common target in the course of signalling of FMLF and IL‐3 and activation by A23187.…”

Sequential Metal Catalysis towards 7‐Oxostaurosporine and Its Non‐Natural Septanose Analogue

“…In this scenario, installation of the 1 st glycosidic bond can be accomplished by the unprecedented Pd 0 ‐catalyzed asymmetric addition of indolocarbazole 1 [16] to alkoxyallene. The following Ru‐catalyzed RCM [17] and olefin migration would provide a key intermediate 2 , which possesses endo enol ether in a juxtaposition to the remaining N−H bond of indolocarbazole towards Pd II ‐catalyzed oxidative cyclization [18] to form the bicyclic skeleton of indolocarbazole pyranoglycoside.…”

In silico and in vitro research of potential antineoplastic amino acid derivatives of indolocarbazol glycosides properties

“…В этом классе молекулы, содержащие гетероциклическое ядро индоло [2,3-а] пирроло [3,4-с] карбазола, обладают, наряду с антибактериальным, противопаразитарным и прочими видами биологической активности, наиболее выраженным противоопухолевым действием [1]. Оно обусловлено их способностью интеркалировать в ДНК, ингибировать топоизомеразы 1 и 2 [2,3], протеинкиназы С и А [2,4], циклинзависимые киназы [5]. В настоящее время проходят II-III фазы клинических испытаний разработанные на основе соединений этого класса производные противоопухолевого антибиотика ребеккамицина эдотекарин и бекатекарин, производное алкалоида стауроспорина мидостаурин [6].…”