We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines.
The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50values ( 3 > 2 > 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging.
Proceedings of the National Academy of Sciences of the United States of America. 2016 Apr 04 [Epub ahead of print]
Melanie Pribisko, Joshua Palmer, Robert H Grubbs, Harry B Gray, John Termini, Punnajit Lim
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;, Verrix, LLC, Pasadena, CA 91107;, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125; Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010, Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010.