title: Synthesis, cytotoxicity and antitumor activity of platinum(II) complexes of cyclopentanecarboxylic acid hydrazide.
abstract: New platinum(II) complexes of cyclopentanecarboxylic acid hydrazide (cpcah) were prepared, characterized by elemental analysis, IR and 1H NMR spectra, and evaluated for in vitro cytotoxicity in Friend leukemia (FL) and A2780 ovarian tumor cells, induction of apoptosis in FL cells, as well as for in vivo antitumor activity toward murine L1210 leukemia and Lewis lung carcinoma. The spectral analyses indicated a cis-square planar structure of the complexes with hydrazide ligand coordinated via the NH2 group. The compounds exerted significantly lower in vitro and in vivo toxicities as compared with those of cisplatin (cis-diamminedichloroplatinum(II), DDP). On the other hand, the complex [Pt(NH3)(cpcah)Cl2] exhibited antitumor activity against L1210 leukemia in mice comparable to that of cisplatin, resulting at a dose of 42 mg/kg (administered 3 times) in a T/C (mean survival time) of 280%. This compound displayed an in vitro macromolecular synthesis inhibition pattern similar to that of DDP. At concentrations close to the cytostatic ones (10-20 microM) this complex, as well as DDP, was able to induce apoptosis in FL cells as shown by neutral comet assay and morphological analysis. We concluded that there is a correlation between the ability of platinum complexes to induce apoptosis and their antitumor activity.
authors.affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia.
authors.forename: D
authors.initials: D
authors.lastname: Kushev
authors.forename: G
authors.initials: G
authors.lastname: Gorneva
authors.forename: S
authors.initials: S
authors.lastname: Taxirov
authors.forename: N
authors.initials: N
authors.lastname: Spassovska
authors.forename: K
authors.initials: K
authors.lastname: Grancharov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000188:drug therapy; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D011506:Proteins; C403251:amminedichloro(cyclohexanecarboxylic acid hydrazide)platinum(II); D002945:Cisplatin