New insights on the antitumoral properties of prodiginines.
Apoptosis is involved in the action of several (and perhaps all) cancer-chemotherapeutic agents. Prodiginines are a family of natural red pigmented secondary metabolites, produced by different bacteria and most of them are characterized by a common pyrrolylpyrromethene skeleton. The biosynthesis of prodigiosin and derivatives has been extensively studied in Serratia marcescens. S. marcescens is a Gramnegative bacterium belonging to Enterobacteriaceae. Prodiginines show numerous biological activities pointing out immunosuppressive and anticancer properties. Some prodiginines displayed apoptotic effects in vitro and antitumor activity in vivo. Their cytotoxic effect is attributed to the presence of the C- 6 methoxy substituent. The A-pyrrole ring plays a key role in both the copper nuclease activity and the cytotoxicity of prodiginines. Here we review the main characteristics of prodigiosin and their derivatives as well as the most prominent pharmacological activity of prodiginines and related compounds, including novel synthetic PG-derivatives with lower toxicity like GX15-070 (Obatoclax). The molecular targets of prodiginines are discussed and the mechanism of action for these molecules is a current topic in biomedicine with a real therapeutica potential in the clinic.
Pérez-Tomás
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Department of Pathology and Experimental Therapeutics, Cancer Cell Biology Research Group, Universitat de Barcelona. Pavelló Central, 5a Planta, LR 5101 C/Feixa Llarga s/n, E 08907 L'Hospitalet de Llobregat, Barcelona, Spain. rperez@ub.edu
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D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D007211:Indoles; D009369:Neoplasms / Q000188:drug therapy; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D011758:Pyrroles / Q000633:toxicity; D012705:Serratia / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C010307:prodiginine; D011353:Prodigiosin; C520962:obatoclax