Anticancer and immunosuppressive properties of bacterial prodiginines.
Bacterial prodiginines are a family of red-pigmented, tripyrrolic compounds that display numerous biological activities, including antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive and anticancer properties. Recently, significant progress has been made in understanding the biosynthesis and regulation of bacterial prodiginines. An understanding of the biosynthesis of prodiginines will allow engineering of bacterial strains capable of synthesizing novel prodiginines through rational design and mutasynthesis experiments. Bacterial prodiginines and synthetic derivatives are effective proapoptotic agents with multiple cellular targets, and they are active against numerous cancer cell lines, including multidrug-resistant cells, with little or no toxicity towards normal cell lines. A synthetic derivative, GX15-070 (Obatoclax), developed through structure-activity relationship studies of the pyrrolic ring A of GX15, is in multiple Phase I and II clinical trials in both single and dual-agent studies to treat different types of cancer. Therefore, prodiginines have real therapeutic potential in the clinic.
University of Cambridge, Department of Biochemistry, Tennis Court Road, UK. nrw26@mole.bio.cam.ac.uk
Neil R
NR
Williamson
Peter C
PC
Fineran
Tamzin
T
Gristwood
Suresh R
SR
Chawrai
Finian J
FJ
Leeper
George P C
GP
Salmond
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; C010307:prodiginine; D011353:Prodigiosin