In vitro anticancer activities and optical imaging of novel intercalative non-cisplatin conjugates.

The first pi-conjugated macrocyclic diimine and triaza DNA-binding intercalators and their platinum(II) conjugates have been synthesized by direct Schiff base cyclocondensation. The in vitro anticancer activities of compounds 3, 4, and 5 were tested on five cancer cell lines: MCF-7, A549, P388, A2780, and A2780cisR. Ovarian tumors were included specifically to evaluate the new conjugates' ability to circumvent A2780cisR resistance. Antitumor effects of the newly conjugated compounds were compared to those of cisplatin. The data clearly indicate that improved drug efficiencies are achieved as a result of the intercalative moieties. The luminescent probe that was integrated in complexes 8-10 made it possible to monitor drug penetration using optical imaging. Enhanced targeting of tumor nuclei by the study compounds was confirmed by confocal microscopy. This paper describes a new class of platinum-based antitumorals differing from cisplatin in several critical aspects with the potential for significantly improving clinical outcomes in cancer patients.