Search

A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC50 values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.

The appropriate 1-arylhydrazinecarbonitriles 1a&ndash, c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a&ndash, c, which are subsequently converted into the corresponding amides 4a&ndash, e, 8a&ndash, c, sulfonamides 5a&ndash, n, 9, ureas 6a&ndash, I, and thioureas 7a&ndash, d. The structures of the newly prepared derivatives 3a&ndash, c, 4a&ndash, e, 5a&ndash, n, 6a&ndash, i, 7a&ndash, d, 8a&ndash, c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1&prime, biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC50 values in the range of 2.38&ndash, 3.77 &mu, M. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.

The reaction of bidentate 1-(pyridin-2-yl)-2,3,7,8-tetrahydro-1H-imidazo[2,1-b][1,3,5]triazepin-5(6H)-one ligands (3a–g) with copper(II) chloride, carried out at ambient temperature in aqueous EtOH or DMF, led to the formation of corresponding complexes 4 of type [Cu(L)(Cl)2], which in the presence of water and excess of Cu2+ ions provided copper(II) complexes (5) of tridentate N1-[1-(pyridin-2-yl)imidazolidin-2-ylidene]ethane-1,2-diamine ligands of the formula {[Cu(L)(μ-Cl)]2Cl2}n. Structures of the selected complexes 4 and 5 were confirmed by single crystal X-ray crystallography. The mechanism of the observed copper(II)-assisted hydrolysis of cyclic ureas 3 was elucidated with the aid of quantum chemical calculations.

Isoquinoline derivatives have attracted great interest for their wide biological and fluorescent properties. In the current study, we focused on the synthesis of a series of novel isoquinoline derivatives substituted at position 3 of the heteroaromatic ring. Compounds were obtained in a Goldberg&ndash, Ullmann-type coupling reaction with appropriate amides in the presence of copper(I) iodide, N,N-dimethylethylenediamine (DMEDA), and potassium carbonate. The structures of novel isoquinolines were confirmed by IR, NMR, and elemental analysis, as well as X-ray crystallography. In the course of our research work, the visible fluorescence of this class of compounds was observed. The above findings prompted us to investigate the optical properties of the selected compounds.

The pyrithione derivative, bis{2-[(1-oxidopyridin-2-yl)sulfanyl]-4,5-dihydro-1H-imidazol-3-ium} tetrachlorocuprate(2-) (1a) has been obtained by the reaction of one equivalent of 2-[(4,5-dihydro-1H-imidazol-2-yl)thio]pyridine 1-oxide hydrochloride with one and a half equivalents of copper (II) chloride dihydrate in methanol in a very good yield. The structure of this product was confirmed by X-ray crystallography, infrared spectroscopy, and elemental analysis.

The guanidine derivative N-{[(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)amino](phenylamino)methylene}benzamide (3) has been obtained by the reaction of one measure of N-{[7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene]carbamothioyl}benzamide (2) with one measure of aniline in the presence of mercury(II) chloride and triethylamine in anhydrous dimethylformamide. The structure of product 3 was confirmed by 1H and 13C-NMR, infrared spectroscopy, and elemental analysis.

A series of 2-imino-2H-chromen-3-yl-1,3,5-triazine compounds 5&ndash, 12, which are namely hybrids of 2,4-diamino-1,3,5-triazines and 2-imino-coumarins, was synthesized by reacting 2-(4,6-diamine-1,3,5-triazin-2-yl)acetonitriles 1&ndash, 4 with 2-hydroxybenzaldehydes. After this, upon heating in aqueous DMF, 2-imino-2H-chromen-3-yl-1,3,5-triazines 10 and 12 were converted into the corresponding 2H-chromen-3-yl-1,3,5-triazines 13 and 14, which are essentially hybrids of 2,4-diamino-1,3,5-triazines and coumarins. The in vitro anticancer activity of the newly prepared compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO and RT-4. The greatest cytotoxic activity displayed 4-[7-(diethylamino)-2-imino-2H-chromen-3-yl]-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-amine (11, IC50 in the range of 1.51&ndash, 2.60 &mu, M).

Six series of structurally different mono- and binuclear copper(II) complexes 5–10 were obtained by reacting N-(2-pyridyl)imidazolidin-2-ones (1a–l), N,N'-bis(2-pyridyl)imidazolidin-2-ones (2a,b), N-acyl-N'(2-pyridyl)imidazolodin-2-ones (3a–j) and N-(2-pyridyl)imidazolidine-2-thiones (4a–g) with copper(II) chloride at an ambient temperature. The coordination modes of the complexes obtained were established by elemental analysis, IR spectroscopic data and single crystal X-ray diffraction studies. The in vitro cytotoxic activities of both the free ligands and copper(II) complexes were evaluated using a crystal violet microtiter plate assay on five human tumor cell lines: LCLC-103H, A-427, SISO, RT-4 and DAN-G. The free ligands 1–4 at concentration attainable in cancer cells of 20 μM showed no meaningful cytotoxic effect with cell viability in the range of 88%–100%. The most potent copper(II) complex of 1-(6-ethoxy-2-pyridyl)imidazolidin-2-one (6b) exhibited selective cytotoxicity against A-427 lung cancer cell line, while the complexes of 1-(5-methyl-2-pyridyl)imidazolidine-2-thione (5h) and 1-(4-tert-butyl-2-pyridyl)imidazolidine-2-thione (5j) showed cytostatic effect against a whole panel of five human tumor cell lines. In conclusion, the only complexes that showed remarkably increased activity in comparison to the free ligands were those obtained from N-(2-pyridyl)imidazolidine-2-thiones 4c and 4e substituted with alkyl group at position 4 or 5 of pyridine ring.