title: Novel soluble cationic trans-diaminedichloroplatinum(II) complexes that are active against cisplatin resistant ovarian cancer cell lines.
abstract: Positively charged, water soluble cis/trans-[PtCl(2)(piperazine)(Am1)] (where Am1 = NH(3), n-butylamine, isopropylamine, 4-picoline, piperidine, and piperazine) has significant cytotoxic activity against cisplatin resistant ovarian cancer cells. The charged complexes are taken up by cancer cells much more rapidly than cisplatin and bind to cellular DNA and to calf thymus DNA much faster than cisplatin or transplatin. The platinum-piperazine complexes bind proteins (ubiquitin and myoglobin) very slowly as compared to cisplatin and to their neutral piperidine analogues. Altogether, the results reported here suggest that combination of positively charged ligands with a trans-Pt(II)Cl(2) center may lead to the discovery of platinum complexes that are able to circumvent cisplatin resistance.
authors.affiliation: Department of Medicinal Chemistry and Natural Products, School of Pharmacy, P.O. Box 12065, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Najajreh
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Perez
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro-Ranninger
authors.forename: Dan
authors.initials: D
authors.lastname: Gibson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002945:Cisplatin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008024:Ligands; D009211:Myoglobin / Q000737:chemistry; D010051:Ovarian Neoplasms; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009211:Myoglobin; D010879:Piperazines; D025801:Ubiquitin; C034697:transplatin; D004247:DNA; D002945:Cisplatin