Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[Pt(L)(2)(ox)] (1), [Pt(2-OMeL)(2)(ox)] (2), [Pt(3-OMeL)(2)(ox)] (3), [Pt(2,3-diOMeL)(2)(ox)] (4), [Pt(2,4-diOMeL)(2)(ox)] (5), [Pt(3,4-diOMeL)(2)(ox)] (6) and [Pt(3,5-diOMeL)(2)(ox)].4H(2)O (7) platinum(II) oxalato (ox) complexes were synthesized using the reaction of potassium bis(oxalato)platinate(II) dihydrate with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). The complexes 1-7, which represent the first platinum(II) oxalato complexes involving adenine-based ligands, were fully characterized by various physical methods including multinuclear and two dimensional NMR spectroscopy. A single-crystal X-ray analysis of [Pt(2,4-diOMeL)(2)(ox)].2DMF (5.2DMF; DMF=N,N'-dimethylformamide), proved the slightly distorted square-planar geometry in the vicinity of the Pt(II) ion with one bidentate-coordinated oxalate dianion and two adenine derivatives (nL) coordinated to the Pt(II) centre through the N7 atom of an adenine moiety, thereby giving a PtN(2)O(2) donor set. In vitro cytotoxicity of the prepared complexes was tested by an MTT assay against osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines. The best results were achieved for the complexes 2 and 5 in the case of both cell lines, whose IC(50) values equalled 3.6+/-1.0, and 4.3+/-2.1microM (for 2), and 5.4+/-3.8, and 3.6+/-2.1microM (for 5), respectively. The IC(50) equals 9.2+/-1.5microM against MCF7 cells in the case of 1. The in vitro cytotoxicity of the mentioned complexes significantly exceeded commercially used platinum-based anticancer drugs cisplatin (34.2+/-6.4microM and 19.6+/-4.3microM) and oxaliplatin (>50.0microM for both cancer cell lines).
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PMID:Platinum(II) oxalato complexes with adenine-based carrier ligands showing significant in vitro antitumor activity. 2030

The reactions of potassium bis(oxalato)platinate dihydrate with two molar equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine; Ros) and its benzyl-substituted analogues, i.e. 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were performed and the [Pt(ox)(Ros)(2)].(3/4)H(2)O (1), [Pt(ox)(2OMeRos)(2)].H(2)O (2), [Pt(ox)(3OMeRos)(2)].(1/2)H(2)O (3) and [Pt(ox)(4OMeRos)(2)].(3/4)H(2)O (4) platinum(II) oxalato complexes were obtained. The methods of the elemental analysis, IR, Raman and NMR spectroscopy, ESI + mass spectrometry, molar conductivity measurement and TG/DTA thermal analysis were performed to characterize the obtained products. The complexes 1-4 involve tetracoordinated central Pt(II) atom with one bidentate-coordinated oxalate dianion (ox) and two monodentate adenine-based molecules (nRos), thus giving the square-planar geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa, A2780cis and, except for 2, also against HOS cancer cells. The complex 1 was also tested for its cytotoxicity in primary cultures of human hepatocytes and it was not found to be hepatotoxic up to the concentration of 50.0 microM.
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PMID:Roscovitine-based CDK inhibitors acting as N-donor ligands in the platinum(II) oxalato complexes: preparation, characterization and in vitro cytotoxicity. 2069 37