The prodigiosins, proapoptotic drugs with anticancer properties

The family of natural red pigments, called prodigiosins (PGs), characterised by a common pyrrolylpyrromethene skeleton, are produced by various bacteria. Some members have immunosuppressive properties and apoptotic effects in vitro and they have also displayed antitumour activity in vivo. Understanding the mechanism of action of PGs is essential for drug development and will require the identification and characterisation of their still unidentified cell target. Four possible mechanisms of action have been suggested for these molecules: (i) PGs as pH modulators; (ii) PGs as cell cycle inhibitors; (iii) PGs as DNA cleavage agents; (iv) PGs as mitogen-activated protein kinase regulators. Here, we review the pharmacological activity of PG and related compounds, including novel synthetic PG derivatives with lower toxicity and discuss the mechanisms of action and the molecular targets of those molecules. The results reported in this review suggest that PGs are a new class of anticancer drugs, which hold out considerable promise for the Pharmacological Industry. (C) 2003 Elsevier Inc. All rights reserved.