- Synthesis, characterization, lipophilicity and cytotoxic properties of novel bis(carboxylato)oxalatobis(1-propylamine)platinum(IV) complexes
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A series of novel bis(carboxylato)oxalatobis(1-propylamine)platinum(IV) complexes as well as an ethylamine analog were synthesized. The compounds are either symmetrical with both axial ligands consisting of monoesters of succinic acid, or unsymmetrical, with one axial ligand being acetate. The compounds were characterized in detail by elemental analysis, mass spectrometry and multinuclear (1H, 13C, 15N, 195Pt) NMR spectroscopy. The reduction behavior was followed by NMR spectroscopy, while lipophilicity was determined by analytical reversed-phase HPLC measurements. The capacity of inhibiting proliferation of the human cancer cell lines A549 (non-small cell lung cancer), CH1(PA-1) (ovarian teratocarcinoma) and SW480 (colon carcinoma) was evaluated by the MTT assay. In the most sensitive cell line CH1(PA-1), all compounds exhibited IC50 values in the lower μM range. In general, the IC50 values decreased with increasing lipophilicity within the two compound series. Nevertheless, replacing one of the succinic ester ligands with acetate has a rather marginal impact on antiproliferative activity and is hardly disadvantageous.
- Hizal, Selin,Hejl, Michaela,Jakupec, Michael A.,Galanski, Markus,Keppler, Bernhard K.
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- Bis- and Tris(carboxylato)platinum(IV) Complexes with Mixed Am(m)ine Ligands in the trans Position Exhibiting Exceptionally High Cytotoxicity
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A series of seven diam(m)inebis(carboxylato)dihydroxidoplatinum(IV) and eleven diam(m)inetris(carboxylato)hydroxidoplatinum(IV) complexes with am(m)ine ligands in the trans position was synthesized and characterized by multinuclear 1H, 13C, 15N, 195Pt NMR spectroscopy. IC50 values for all eighteen substances were determined by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for three human cancer cell lines. In cisplatin-sensitive CH1(PA-1) cancer cells, diam(m)inebis(carboxylato)dihydroxidoplatinum(IV) complexes displayed 50 % inhibitory concentrations in the micromolar range, whereas for the most lipophilic compounds of the diam(m)inetris(carboxylato)hydroxidoplatinum(IV) series, promising IC50 values in the nanomolar range were found.
- Hoffmeister, Bj?rn R.,Hejl, Michaela,Jakupec, Michael A.,Galanski, Markus,Keppler, Bernhard K.
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p. 1700 - 1708
(2015/04/14)
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- Optimization of gefitinib analogues with potent anticancer activity
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The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.
- Yin, Kai-Hao,Hsieh, Yi-Han,Sulake, Rohidas S.,Wang, Su-Pei,Chao, Jui-I.,Chen, Chinpiao
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supporting information
p. 5247 - 5250
(2015/01/08)
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- INDAZOLE COMPOUNDS
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Indazole compounds, processes for their preparation, pharmaceutical compositions containing such compounds and their use in therapy.
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Page/Page column 30
(2012/03/26)
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- Acetyl bromide-alcohols as convenient reaction systems for: a) Removal of N-tert-Boc, N-Cbz and N-Ac protective groups, b) Esterifications and transesterifications, c) Debenzylation of aryl-O-benzyl ethers
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Hydrogen bromide generated in situ by the addition of acetyl bromide to alcohols is a useful reagent for esterifications and transesterifications; N- tert-Boc, N-Cbz, and N-Ac deprotections; and debenzylation reactions.
- Lesk,Nudelman
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p. 1405 - 1408
(2007/10/03)
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- Synthesis and investigation of N4-substituted cytarabine derivatives as prodrugs.
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Esters of Cytarabine-N4-carboxylates 2a-i and succinamates 3a-f were synthesized as prodrugs of cytarabine (Ara-C) with the aim of developing improved derivatives for oral or parentral administration. At pH 2 series 2 showed relative higher stability than 3, while both series of esters revealed matched stability at pH 7. All esters were susceptible to enzymatic hydrolysis by rat plasma and liver homogenate with half lives ranged from 0.14 h to 12 d, and showed improved stability against cytidine deaminase. A parabolic relation was shown between Kobs of enzymatic hydrolysis and Vw. All compounds are more lipophilic than the parent drug, Ara-C.
- Fadl,Hasegawa,Youssef,Farag,Omar,Kawaguchi
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p. 382 - 387
(2007/10/02)
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