Trans-platinum complexes as anticancer drugs: recent developments and future prospects.
Cisplatin represents one of the most potent drugs available in the cancer chemotherapy for several solid tumors, such as germ cell tumors, ovarian, lung, head and neck, and bladder cancers. Structure-activity relationship studies showed that leaving groups (generally chlorine) and two amine ligands in platinum complexes must be in the cis orientation and that the corresponding trans compounds are inactive. During the 1990's, several groups have reported trans-platinum compounds with in vitro growth inhibitory and in vivo antitumor properties. Some of these complexes were active against tumor cells resistant to cisplatin. More interestingly, there is a difference in cellular and biochemical pharmacology between trans-platinum complexes and cisplatin. Thus, monofunctional adducts might be related to the cytotoxicity of the trans-platinum-iminoether compounds against cis-DDP sensitive/resistant cell lines; unusual structure of long-range interstrand cross-links might be relevant for great effectivity of bifunctional polinuclear trans-platinum(II) compounds against cis-DDP resistant variants. Trans-platinum compounds, appear to follow different pattern of cell killing in comparison to cisplatin, thus giving a reason for optimism in their development as a new class of platinum-based antitumor drugs.
Radulovic
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Dept. Drug Development, Institute for Oncology and Radiology of Serbia, Pasterova 14, Belgrade, 11000, Yugoslavia. sinisar@ncrc.ac.yu
Tesic
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Z
Manic
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D000818:Animals; D000970:Antineoplastic Agents; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA