Two novel zinc phthalocyanines (Pcs): tetramethyl tetrakis-2,(3)-[(4-methyl-2-pyridyloxy)phthalocyaninato] zinc(II) (4) and (the negatively charged form) tetrakis-2,(3)-[(3-carboxylicacid-6-sulfanylpyridine)phthalocyaninato] zinc(II) (5), water soluble by virtue of their ionic substituent groups were synthesized. The spectroscopic properties of both compounds were determined and their photodynamic activities were investigated in a human tumor cell model. In aqueous media the two peripherally substituted water soluble Pcs are highly aggregated. The phototoxic activity of the two novel Pcs (Pc 4 and Pc 5; 0-20 μM) was shown to be time- and dose-dependent in human pancreatic carcinoid BON cells, leading to a reduction of tumor cells of >80% compared to the controls. The effectiveness of the treatment appeared to be attenuated by the aggregation of Pcs under aqueous conditions. Interestingly, even those cells that were not immediately killed by the photoactivated photosensitizer seemed to be affected by the Pc photodynamic activity, as a single PDT induced long-lasting effects on cell survival. Even 4 days after PDT, the number of surviving cells did not re-increase or still dropped, as compared to control cells. The underlying mechanism of this observation has to be deciphered in future investigations.

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Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment. Animacroxam consists of an HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency. Animacroxam revealed pronounced antiproliferative, cell-cycle arresting, and apoptosis-inducing effects in TGCT cell lines with different cisplatin sensitivities. The IC values of animacroxam ranged from 0.22 to 0.42 μmol/L and were not correlated to the cisplatin sensitivity of the tumor cells. No unspecific cytotoxicity of animacroxam was observed in either cisplatin-sensitive or resistant TGCT cells, even at doses as high as 10 μmol/L. Furthermore, animacroxam induced the formation of actin stress fibers in cancer cells, thereby confirming the cytoskeleton-disrupting and antimigratory properties of its imidazole moiety. When compared with the clinically established HDAC inhibitor vorinostat, the novel dual-mode compound animacroxam exhibited superior antitumoral efficacy Animacroxam also reduced the tumor size of TGCT tumors, as evidenced by performing xenograft experiments on tumor bearing chorioallantoic membranes of fertilizes chicken eggs (CAM assay). The experiments also revealed a very good tolerability of the compound, and hence, animacroxam may be a promising candidate for innovative treatment of TGCT in general and the more so for platinum-insensitive or refractory TGCT..