Marine pyrrolocarbazoles and analogues: synthesis and kinase inhibition.
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.
Deslandes
Sébastien
S
Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, Toulouse Cédex 9, France. deslandes@chimie.ups-tlse.fr
Chassaing
Stefan
S
Delfourne
Evelyne
E
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000071877:Checkpoint Kinase 1; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008386:Marine Biology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000470:Alkaloids; D002227:Carbazoles; D007093:Imidazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C433587:granulatimide; C116644:isogranulatimide; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1