title: Anticancer activity and tissue distribution of platinum (II) complex with lignin-derived polymer of benzene-poly-carboxylic acids.
abstract: Platinum-containing antineoplastic agents with physiologically active ligands seem to be a promising direction in anticancer drug design. PDBA is a novel promising antineoplastic agent, containing polymer ligand of natural origin (international patent WO2013/143549 A1). Polymer ligand of PDBA has a highly functionalised polyphenolic backbone, which exerts its own pharmacological effect via immune modulation and regulation of gene expression. PDBA is a cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands (approximate bulk formula C83H70N2O27Pt). The agent is being evaluated in Phase II controlled clinical trials in metastatic breast cancer patients. In the present study, tissue distribution and tumour growth inhibition effects of PDBA, cisplatin and carboplatin were compared in SHR female mice, bearing inoculated solid Ehrlich carcinoma. The agents were administered subcutaneously every second day for the period of 10days (5 injections) at 62.5mg/kg, 3.0mg/kg and 18.5mg/kg for PDBA, cisplatin and carboplatin, respectively. Experimental animals were sacrificed on the Days 11, 16 and 23 after the inoculation of the tumour. The doses of all studied drugs were selected to obtain similar antitumour efficacy with ca. 50% growth inhibition of the Ehrlich tumour at the end of the study. The efficacy of a single platinum reactive moiety [cis-diammineplatinum(II)] was shown to be the highest for cisplatin, followed by PDBA and finally carboplatin. However, the toxicity of PDBA was considerably lower than that of carboplatin and especially cisplatin. The drugs were mainly distributed in lungs, kidneys, liver, spleen and tumour tissue. PDBA showed quite high accumulation in the tumour tissue, possibly, owing to the effect of the lignin-derived ligand.
authors.affiliation: Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russian Federation. Electronic address: n.solovyev@spbu.ru.
authors.forename: Nikolay D
authors.initials: ND
authors.lastname: Solovyev
authors.affiliation: RD Pharm LTD, St. Petersburg, Russian Federation; N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Fedoros
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation; Institute of Toxicology of Federal Medico-Biological Agency, St. Petersburg, Russian Federation.
authors.forename: Evgenii J
authors.initials: EJ
authors.lastname: Drobyshev
authors.affiliation: Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russian Federation; Institute of Toxicology of Federal Medico-Biological Agency, St. Petersburg, Russian Federation.
authors.forename: Natalya B
authors.initials: NB
authors.lastname: Ivanenko
authors.affiliation: RD Pharm LTD, St. Petersburg, Russian Federation; N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Pigarev
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Tyndyk
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Anisimov
authors.affiliation: Russian Scientific Centre 'Applied Chemistry', St. Petersburg, Russian Federation.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Vilpan
authors.affiliation: RD Pharm LTD, St. Petersburg, Russian Federation; N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Panchenko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D001554:Benzene / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000737:chemistry*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002945:Cisplatin / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D008031:Lignin / Q000737:chemistry*; D051379:Mice; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000627:therapeutic use; D010984:Platinum / Q000737:chemistry*; D011108:Polymers / Q000032:analysis* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009944:Organoplatinum Compounds; D011108:Polymers; D010984:Platinum; D008031:Lignin; D016190:Carboplatin; D001554:Benzene; D002945:Cisplatin
keywords: Antineoplastic; Benzene-poly-carboxylic acids; Breast cancer; Non-clinical studies; Platinum; Tissue distribution; tumour suppression