Synthesis and antiproliferative activity in vitro of new pyrido[1,4-b]diazepine derivatives and imidazo[4,5-b]pyridine.

A novel series of esters 8-10 and hydrazones 4-6 was synthesized from 4-aryl-2-phenacylidene-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepine (1-3). Subsequent treatment of hydrazone 4 with p-chlorbenzaldehyde furnished azine 7. Long-standing heating of ester 8 with hydrazine hydrate afforded 3-[1-(p-chlorophenylene)-2-(5-phenyl-1H-pyrazol-3-yl)-ethyl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one (11).

Synthesis and in vitro antiproliferative activity of new 1,3-(oxytetraethylenoxy)-cyclotriphosphazene derivatives.

A new series of 1,3-(oxytetraethylenoxy)-cyclotriphosphazene derivatives containing aziridine or salicylaldehyde (2-hydroxybenzaldehyde) or its Schiff base units after condensation with 2-chloroethylamine and anthraquinone groups as co-substituents has been synthesized. Their cytostatic activity in vitro against the HL-60, A549 and HCV29T cancer cell lines has been studied. Some of the compounds exhibited antiproliferative activity in the range of the international criteria for synthetic agents (4 microg/ml) against the cell lines being tested.

Synthesis and antiproliferative activity of some 5-substituted 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles.

A series of new 5-substituted 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles has been synthesised and evaluated for their antiproliferative activity. The compounds were prepared by the reaction of the sulphinylbis(2,4-dihydroxythiobenzoyl) (STB) wit hydrazides or carbazates. The panel substitution included alkyl, alkoxy, aryl and heteroaryl derivatives.

Synthesis and in vitro antileukemic activity of some new 1,3-(oxytetraethylenoxy)cyclotriphosphazene derivatives.

A new series of 1,3-(oxytetraethylenoxy)cyclotriphosphazene derivatives bearing 2-chloroethylamine or salicylaldehyde (2-hydroxybenzaldehyde) or its Schiff base (after condensation with 2-chloroethylamine) units and having also 2-naphthyl or anthraquinone groups as cosubstituents has been synthesized. The in vitro cytotoxic activity of these compounds against a panel of four cancer cell lines has been studied. Most of the compounds exhibited antiproliferative activity in the range of the international criterion for synthetic agents (4 microg/mL) against the MOLT4, L 1210, HL-60, and P388 cell lines chosen for testing.

Synthesis of 5,6-dimethyl-9-methoxy-1-phenyl-6H-pyrido[4,3-b]carbazole derivatives and their cytotoxic activity.

Starting from 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine 7 and mixed anhydrides of 4-nitrobenzoic acid or 4-methoxybenzoic acid, the corresponding 5,6-dimethyl-9-methoxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 11a-b, 5,6-dimethyl-9-hydroxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 12a, 12c, and their quaternary salts 13a-d were obtained. The four new pyridocarbazole derivatives 12a-c and 13d satisfy the international activity criterion for synthetic compounds, namely an ID(50) value lower then 4 microg/mL in preliminary in vitro cytotoxic activity screening against the A549 cell line (non-small cell lung cancer).

Magnesium deficiency inhibits primary tumor growth but favors metastasis in mice.

The results of several experimental and epidemiological studies have shown an inverse correlation between Mg status and the risk of some cancers. However, relationship between magnesium and cancer is complex. The aim of our work was to examine the precise effect of Mg deficiency on transplantable mouse tumor growth and metastasis.

Synthesis and in vitro cytostatic activity of some new 1,3-(oxytetraethylenoxy)-cyclotriphosphazatriene derivatives.

A series of cyclophosphazene crown ether derivatives bearing aziridinyl (ethylene imine) units and also 2-naphthyl or anthraquinone groups as co-substituents has been synthesized and their cytostatic activity against the panel of eight cancer cells in vitro has been studied. The substituents used exhibit different activities: alkylation (aziridinyl groups) and intercalation (naphtyl, anthraquinone groups) against DNA. These both interactions are supposed to enhance the efficiency of the cyclophosphazene crown ether derivatives studied as cytotoxic agents.

Synthesis, structure, and cytostatic properties of new olivacine derivatives.

Starting from 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine and 6-methylpicolinic acid, 9-methoxy-5-methyl-1-(6-methylpyridin-2-yl)-6H-pyrido[4,3-b]carbazole 10 and its 6-alkylderivatives 12-17 were obtained. The newly obtained compounds showed significant cytostatic activity against cultured L1210 cells and high cytotoxicity towards various human tumor cell lines.

Role of copper in tumour angiogenesis--clinical implications.

The formation of new blood vessels is the initial step in progressive tumour development and metastasis. The first stage in tumour angiogenesis is the activation of endothelial cells. Copper ions stimulate proliferation and migration of endothelial cells.

Synthesis and antiproliferative activity in vitro of 2-aminobenzimidazole derivatives.

A novel series of Schiff bases 1-11, the derivatives of 2-aminobenzimidazole and substituted aromatic aldehydes, has been synthesised. Compounds 1-11 reduced by NaBH(4) formed 2-benzylaminobenzimidazoles 12-21. 2-(o-Bromobenzylamino)benzimidazole (15) acylated by cinnamoyl chloride gave 2-(o-bromobenzylamino)-1-cinnamoylbenzimidazole (22).

Multinuclear NMR spectroscopy and antitumor activity of novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines.

Novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N, 195Pt). The complexes are of two types: [PtCl2(L)2] and [PtCl2(NH3)(L)], where L=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) and 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp). Significant 15N NMR upfield shifts (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site.

[The role of copper in tumor angiogenesis--clinical implications].

This review concerns a brief introduction into the basics of tumor blood vessels development as well as the regulatory mechanisms of this process. The role of copper ions in tumor angiogenesis is discussed. The new antiangiogenic therapies based on a reduction of copper level in tumor microenvironment are reviewed.