Novel gallium(III) complexes containing phthaloyl derivatives of neutral aminoacids with apoptotic activity in cancer cells

The reaction of N-phthaloylglycine and N-phthaloyl-dl-alanine with trimethylgallium (1:1) yielded the dinuclear complexes [Me2Ga(μ-O2CCH2N(CO)2C6H4)]2 (1) and RS-[Me2Ga(μ-O2CCHMeN(CO)2C6H4)]2 (2), respectively. The molecular structure of 2 was determined by X-ray diffraction studies. The cytotoxic activity of the organogallium(III) complexes (1 and 2) was tested against human tumour cell lines 8505C anaplastic thyroid cancer, A253 head and neck tumour, A549 lung carcinoma, A2780 ovarian cancer, DLD-1 colon carcinoma and compared with that of cisplatin. The best response of the synthesized gallium complexes, compared with that of cisplatin, was observed against 8505C anaplastic thyroid cancer and DLD-1 colon carcinoma, while the best IC50 values were found for A253 head and neck carcinoma. While the studied carboxylic acids show no proliferative activity, complexes 1 and 2 present very similar cytotoxic activity against all the studied cancer cell lines (IC50 from ca. 5 to 25 μM). The cytotoxicities of complexes 1 and 2 are in all cases higher than that presented by gallium(III) nitrate. In addition DNA laddering method showed that treatment of the studied cell lines with IC90 doses of 1 and 2 resulted in the induction of apoptotic mode of cell death.