Studies on the Complexation of Platinum(II) by Some 4-Nitroisoxazoles and Testing the Cytotoxic Activity of the Resulting Complexes.

Two novel platinum(II) complexes (1 and 2) were synthesized by the reaction of the appropriate 3,5-dimethyl-4-nitroisoxazole with K2PtCl4 and characterized by elemental analysis, ESI MS spectrometry, 1H NMR and far-IR spectroscopy. The structure of trans complex 2 was additionally confirmed by X-ray diffraction. The cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) in both normoxia and hypoxia conditions. LogPs of complexes were measured using the shake-flask method. The trans complex 2 showed much better cytotoxic activity than cisplatin for all the tested cancer cell lines. Cis complex 1 was inferior to its trans isomer against all the cancer lines tested in normoxia conditions but proved superior to the reference cisplatin against the MCF-7 and A549 lines, and showed similar activity to cisplatin against the ES-2 line. To gain additional information that may facilitate the explanation of the pharmacological activity of the tested compounds, cellular platinum uptake and stability in L-glutathione solution were determined for both compounds 1 and 2.

Synthesis of Platinum(II) Complexes with Some 1-Methylnitropyrazoles and In Vitro Research on Their Cytotoxic Activity.

A series of eight novel platinum(II) complexes were synthesized by the reaction of the appropriate 1-methylnitropyrazole derivatives with K2PtCl4 and characterized by elemental analysis, ESI MS spectrometry, 1H NMR, 195Pt NMR, IR and far IR spectroscopy. Thermal isomerization of cis-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 1 to trans-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 2 has been presented, and the structure of the compound 2 has been confirmed by X-ray diffraction method. Cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) and their logP was measured using a shake-flask method. The trans complex 2 showed better antiproliferative activity than cisplatin for all the tested cancer cell lines. Additionally, trans-dichloridobis(1-methyl-5-nitropyrazole)platinum(II) 4 has featured a lower IC50 value than reference cisplatin against MCF-7 cell line. To gain additional information that may facilitate the explanation of the mode of action of tested compounds cellular platinum uptake, stability in L-glutathione solution, influence on cell cycle progression of HL-60 cells and ability to apoptosis induction were determined for compounds 1 and 2.

Synthesis of new 1-phenyl-6H-pyrido[4,3-b]carbazole derivatives with potential cytostatic activity.

A number of new 1-substituted-6H-pyrido[4,3-b]carbazole derivatives have been synthesized. Nine of the newly obtained compounds were subjected to preliminary in vitro cytostatic activity screening against murine leukemia (L1210), human lung cancer (A549) and human colon cancer (HT29) cell lines. One particular compound 6f exhibited over 20 times better activity against L1210 tumor cell line than the reference ellipticine.

Synthesis and structure-activity relationship analysis of new olivacine derivatives.

The number of 3'- and 4'-substituted 1-phenyl-6H-pyrido[4,3-b]carbazole derivatives have been synthesized and tested biologically. Eleven of the newly obtained compounds were subjected to the preliminary cytostatic screening for their activity against L1210 (murine leukemia), A498 (human kidney cancer), A549 (human lung cancer) and HT29 (human colon cancer) cell lines. Eight of tested derivatives exhibited significant biological activities, which only weakly depended on side chain length and position of the substituent.

Synthesis and anticancer activity of new 1-substituted-6H-pyrido[4,3-b]carbazole derivatives.

This study examines the synthesis and cytostatic activity of new 5,6-dimethyl-1-substituted-6H-pyrido[4,3-b]carbazole derivatives. Their structures were confirmed by (1)H-NMR and elemental analysis. Seven of the new compounds were tested by the SRB method in vitro against human lung cancer (A549) and human kidney cancer (A498) cell lines. Biological tests indicated remarkable cytostatic effects of four compounds tested in comparison with ellipticine and cisplatin as reference drugs. One particular compound 3c was about four times more active on A498 than ellipticine with similar activity on the A549 cell line, and outperformed cisplatin activity on both tumor cell lines.

Synthesis and cytostatic properties of some 6H-Indolo[2, 3-b][1, 8]naphthyridine derivatives.

The new and efficient synthesis of the title heterocyclic ring system is described starting from suitable 2-chloro-1, 8-naphthyridines. The synthesized 6H-indolo[2, 3-b][1, 8]naphthyridine derivatives were tested in vitro on 55 tumor cell lines for their anticancer properties. The presence of the acetylamino moiety at position 3 in the main ring system proved to be crucial for the cytostatic activity of this class of compounds.