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Curr Med Chem Anti-Canc Agents. 2005 Mar;5(2):137-47.
Metal complexes with aromatic N-containing ligands as potential agents in cancer treatment.
Zhao G, Lin H.
Chemistry Department, University of Nankai, Tianjin, 300071, P. R. China.
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.
Technol Cancer Res Treat. 2004 Aug;3(4):335-45.
The impact of technological advances on the evolution of 3D conformal brachytherapy for early prostate cancer.
Nori D, Reddy NM, Vaughan ED Jr, Shemtov MM.
Department of Radiation Oncology, New York Hospital Queens, 56-45 Main Street, Flushing, NY 11355, USA. firstname.lastname@example.org
Permanent implantation of I-125 and Pd-103 seeds is one of the widely used treatment options for the early stage prostate cancer with minimum normal tissue complications and long-term local control of the tumor. This is possible because of several technological advances made in the past decade to better understand the procedural aspects of implantations with the desired clinical outcome and with acceptable morbidities. In addition, with the widespread use of PSA testing, more widely disseminated information about prostate cancer and increased patient awareness, over 70% of patients are diagnosed early with localized disease and therefore are candidates for definitive local therapy. Delineation of soft tissue structures including the prostate, rectum, urethra and bladder has become more accurate with the use of imaging modalities including Ultrasound and MRI, with or without the CT. A re-evaluation of the dosimetric parameters of the radioactive sources has lead to a more precise estimate of the dose delivered to the prostate and the associated critical normal structures. Technological improvements in the post implant dosimetry have helped to understand the factors, which makes an implant a "good implant" or a "poor implant". Intraoperative treatment planning with on line dosimetry is emerging as one of the best approaches for prostate brachytherapy. In addition, better software is now available producing dose-volume histograms with 3D target and normal tissue reconstruction. The combination of seed implant followed by IMRT would provide scope for differentially boosting the regions under-dosed because of uncontrollable and unexpected reasons during the implant and unsuspected micro extensions of the tumor.
J Med Chem. 2005 Dec 15;48(25):7925-31.
Antitumoral activity of non-platinum xanthate complexes.
Friebolin W, Schilling G, Zoller M, Amtmann E.
German Cancer Research Centre, Department D060, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
To establish structure-activity relationships, derivatives of bis(O-alkyldithiocarbonato)platinum(II) complexes were analyzed. Eighteen bis(O-alkyldithiocarbonato) metal complexes were synthesized, and their cytotoxic activity on two human cancer cell lines was compared with the corresponding platinum bis(O-alkyldithiocarbonato) complexes and cisplatin. Complexes were synthesized with palladium, gold, nickel, copper, rhodium, and bismuth. Palladium and bismuth complexes were found to display significant cytotoxic activity. Palladium complexes were most active with up to 10-fold lower IC50 values as compared with the corresponding platinum complexes. The other complexes were only poorly active. Palladium, bismuth, and nickel complexes were more active at pH 6.8 than at pH 7.4. This difference in activity was most pronounced with palladium complexes. A pH of 6.8 and lower has been frequently found in solid tumors. Drugs with such pH dependent activity are supposed to have an improved therapeutic index as compared to drugs that are active irrespective of pH.