Metal Complexes with Aromatic N-Containing Ligands as Potential Agents in Cancer Treatment

Abstract

Cisplatin (cis-Diamminedichloroplatinum(II)) is now clinically used as one of the most effective anticancer drugs in the treatment of a variety of human solid tumors, such as genitourinary. Unfortunately, its usefulness is limited due to development of resistance in tumor cells and its significant side effects. Thus, a continuing effort is being made to develop analogs to overcome the above shortcomings. However, direct structural analogs of cisplatin have not shown greatly improved clinical efficacy in comparison with the parent drug. The explanation for this finding is that all cis-[PtX(2)(amine)(2)] compounds have shown similar DNA-binding modes, thereby resulting in similar biological consequences. One approach is to look beyond structure-activity on the basis of cisplatin analogs antitumor agents, by identifying novel materials that can be utilized as building blocks. These may have DNA binding modes quite different from that of cisplatin. The introduction of such aromatic N-containing ligands as pyridine, imidazole and 1,10-phenanthroline, and their derivatives (whose donor properties are somewhat similar to the purine and pyrimidine bases) to antitumor agents is drawing attention. Many platinum and non-platinum metal complexes such as palladium, ruthenium, rhodium, copper, and lanthanum, with these aromatic N-containing ligands, have shown very promising antitumor properties in vitro and in vivo in cisplatin-resistant model systems or against cisplatin-insensitive cell lines. For example, one Ru(III) compound, [ImH][trans-Cl(4)(Me(2)SO)(Im)Ru(III)] (Im = imidazole, NAMI-A) successfully entered phase I clinical trials. In this review, medicinal chemistry, DNA binding modes, and the development status of these metal complexes are discussed.

Iron(III) Pincer Complexes as a Strategy for Anticancer Studies

“…The most representative coordination ruthenium-based complexes are KP1019 and NAMI-A, which have entered phase II clinical trials. [2][3][4][5][6][7] The structures of organometallic ruthenium compounds are more diverse. Among them, a series of arene-ruthenium complexes such as RM175, RAPTA-C, RAED-C, and UNICAM-1 have shown very promising therapeutic effects.…”

The Ruthenium Complex cis-(Dichloro)tetraammineruthenium(III) Chloride Presents Selective Cytotoxicity Against Murine B Cell Lymphoma (A-20), Murine Ascitic Sarcoma 180 (S-180), Human Breast Adenocarcinoma (SK-BR-3), and Human T Cell Leukemia (Jurkat) Tumor Cell Lines

“…Ruthenium compounds present some differences related to their mechanisms of action when compared to platinum compounds [8,18,19]; they bind preferentially to proteins [20] and also bind firmly to DNA nucleobases [5,21,22], modifying their conformation, and unwinding DNA. Ruthenium compounds coordinate preferentially to isolated guanine bases [13], leading to extensive DNA cleavage [23] that correlates with high cytotoxicity [24,25].…”

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: Molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

“…In this respect, significant efforts have been made to prepare some promising cis-and trans-Pd(II) complexes with a good in vitro cytotoxicity [9], using (i) aromatic N-donor molecules [10], (ii) dithiocarbamates [8], (iii) dithiocarbazates [11] and (iv) thiosemicarbazones [12] as ligands. The latter two ligands are N,S-donor systems, a combination of donor atoms that was postulated as being particularly suitable to prepare active Pd(II) complexes [13].…”