New complexes of Pt(II) which represent potential third-generation anti- tumor drugs will be prepared and compared to the widely used drug cisplatin, cis-Pt(NH3)2Cl2 and its second-generation analogs. The principal objectives are to find new complexes which do not show cross- resistance in tumors which are resistant to cisplatin. Carrier ligands to be used in preparing the complexes will include heterocyclic amines such as thiazole and imidazole derivatives which have their own biological activities. Tethered ligands in which quinolinium ions with anti-tumor activity are linked to the carrier ligands through flexible chains will also be studied. Possible intercalators may also be used in preparation of complexes with tethered ligands. Variations in leaving groups will be used to improve the aqueous solubilities of the complexes. Related complexes with other metals such as Rh, Ir, Au, and Ru will be prepared and all will be screened for cytotoxicity. Complexes will be characterized by spectroscopic and X-ray diffraction methods. The interactions of the complexes will be studied with nucleobases, sulfur-containing reagents, DNA, and cell membranes.
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