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.
Curr Med Chem. 2010;17(21):2222-31. doi: 10.2174/092986710791331103.
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.
细胞凋亡参与了几种（也许是所有）癌症化疗药物的作用。普洛色林是一类天然红色色素次生代谢产物，由不同的细菌产生，其中大多数的特征在于一个共同的吡咯并吡咯甲川骨架。灵菌红素和衍生物的生物合成在粘质沙雷氏菌中得到了广泛的研究。粘质沙雷氏菌是革兰氏阴性细菌，属于肠杆菌科。普洛色林具有许多生物活性，指出具有免疫抑制和抗癌特性。一些普洛色林在体外表现出凋亡作用，在体内具有抗肿瘤活性。它们的细胞毒性作用归因于 C-6 甲氧基取代基的存在。A-吡咯环在铜核酸酶活性和普洛色林及其衍生物的细胞毒性中起着关键作用。在这里，我们综述了灵菌红素及其衍生物的主要特征，以及普洛色林和相关化合物的最显著的药理学活性，包括新型低毒性的 PG 衍生物如 GX15-070（Obatoclax）。普洛色林的分子靶标被讨论，这些分子的作用机制是当前生物医学领域的一个热门话题，在临床上具有真正的治疗潜力。
