Abstract
Granulatimide and isogranulatimide are alkaloids obtained from marine sources which have been shown to inhibit cell-cycle G2-checkpoint, targeting more particularly checkpoint 1 kinase (Chk1). At a structural level, they possess a characteristic pyrrolocarbazole framework also shared by the well-known rebeccamycin and staurosporine microbial metabolites which have been described to inhibit topoisomerase I and diverse kinases, respectively. This review reports precisely on the synthesis and kinase inhibitory activities of pyrrolocarbazole-based analogues of granulatimide.
Keywords:
granulatimide; indolocarbazole; isogranulatimide; kinase inhibitor; pyrrolocarbazole.
MeSH terms
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Alkaloids / chemical synthesis*
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Alkaloids / chemistry
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Alkaloids / pharmacology
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Carbazoles / chemical synthesis*
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Carbazoles / chemistry
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Carbazoles / pharmacology
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Checkpoint Kinase 1
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology
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Marine Biology
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Protein Kinases / chemistry
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Protein Kinases / metabolism
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology
Substances
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Alkaloids
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Carbazoles
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Imidazoles
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Indoles
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Protein Kinase Inhibitors
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Pyrroles
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granulatimide
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isogranulatimide
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Protein Kinases
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CHEK1 protein, human
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Checkpoint Kinase 1