In Vivo Anticancer Activity of aNontoxic Inert Phenolato Titanium Complex: High Efficacy on Solid Tumors Alone and Combined with Platinum Drugs

摘要

Due to the toxicityofplatinum compounds used in the clinic as anticancer chemotherapies, titanium serves as asafe and at- tractive alternative. Lately,weintroduced anew family of Ti complexes based on readily available phenolato ligands, dem- onstratingincredibly high hydrolytic stability, with the lead compound phenolaTidemonstrating wide cytotoxic activity toward the NCI-60 panel of human cancer cell lines, with an average GI_(50) value of 4.7±2 μm. Herein, we evaluated in vivo: a) the safety,and b) the growth inhibitory capacity (efficacy) of this compound. PhenolaTiwas found to be effective in vivo againstcolon (CT-26) andlung (LLC-1) murine cell lines in syn- geneic hosts and toward ahuman colon cancer (HT-29) cell line in immune-deficient (Nude)mice, with an efficacy similar to that of known chemotherapy.Notably,noclinical signs of toxicitywere observed in the treated mice, namely,noeffect on body weight, spleen weight or kidney function, unlike the effects observed with the positive control Pt drugs.Studies of combinationsofphenolaTi and Pt drugs provided evidence that similarefficacy with decreased toxicitymay be achieved, which is highly valuable for medicinal applications.