- Novel chelate complexes of Co(II), Ni(II), Cu(II), Pd(II) derived from anti- and syn-isomers of 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetic acid with pro-/antiproliferative actions on endothelial cells
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Anti- and syn-isomers of 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetic acid (anti-A and syn-A respectively) were used as potential biologically active polydentate complexing agent for Co2+, Ni2+, Cu2+ and Pd2+ ions for the synthesis of novel complex compounds with directed angiogenesis-correcting action. It shown that the location of functional groups in ligand molecules, the electronic structure of metal as complexing agent and the synthesis conditions affect the localization of coordination bonds and the structure of formed complexes. The interaction of ethanol solutions of metal salts with anti-A and syn-A in an acidic medium at the component ratios M:L = 1:1 and 1:2 leads to the formation of complexes [Co(anti-A)(H2O)3SO4] (1); [Ni(anti-A)(H2O)3SO4] (2); [Cu(anti-A)2Cl2] (3); [Pd(anti-A)2Cl2] (4); [Cu(syn-A)2Cl2] (5); [Pd(syn-A)Cl2] (6) with different coordination of ligands. Coordination mode of ligands identified by IR, UV-Vis, XPS and 1H (13C) NMR spectra. The structures of salt of the anti-A and complexes 1, 2, 6 were determined by X-ray diffraction study. Anti-A is coordinated to metal ions in a chelate manner by the nitrogen atom of the hydroxylimino group and the oxygen atom of the deprotonated carboxyl group. In this case, the 2-aminothiazole fragment does not involve in complexation. Syn-A is coordinated to the central metal ion in neutral form through the nitrogen atoms of hydroxyimino group and thiazole ring. All synthesized complex compounds form stable solutions in neutral medium, which makes it possible to use them as potential biologically active substances. Investigation of biological effects for syn-A shows mitogenic and antiapoptotic activity against endotheliocytes, while anti-A causes inhibition of proliferation almost in the entire concentration range. Complex compounds of Cu2+ and Pd2+ with anti-A and syn-A (3-6) cause an increase of antiproliferative activity of endothelial cells compared with baseline complexing agents. In this case, the activity of complexes with syn-A is superior to activity of analogues with anti-A. The results of cytotoxicity tests revealed a pronounced cytotoxic action for complexes 3 and 4, cytotoxic and proapoptotic activity for 6 and cytostatic effect for 5. For all compounds investigated, a checkpoint from S to G2 has been established, which may indicate DNA replication disturbance or dysregulation in the endogenous signals of the cell cycle of endotheliocytes.
- Orysyk,Zholob,Bon,Nikulina,Orysyk,Nikolaienko,Garmanchuk,Zborovskii, Yu.L.,Tolstanova,Khranovska,Pekhnyo,Vovk
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- Triazolo-pyrimidine intermediates
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There are disclosed a β-lactam compound represented by the formula (I): STR1 wherein R1 represents an acyl group; M represents a hydrogen atom, a protective group of an eliminatable group which is easily hydrolyzable in a human body; B represents a group represented by the formula (b): STR2 where at least one of R2, R3 and R9 represent a group represented by the formula: -A-OR4 where R4 represents a hydrogen or a lower alkyl group; and A represents a straight or branched alkylene group having 1 to 6 carbon atoms; and a remaining group or groups are each independently a hydrogen atom; a cyano group; a lower alkyl group which may be substituted by a halogen atom; a carbamoyl group which may be substituted by a lower alkyl group; a cycloalkyl group; or a carboxyl group which may be substituted by a protective group of an eliminatable group which is easily hydrolyzable in a human body, and also when R9 is -A-OR4, R2 and R3 may be combined with each other to form an alkylene group having 3 to 4 carbon atoms; and Z represents a nitrogen atom or a group represented by the formula: C-R10 where R10 represents a hydrogen atom, a carboxyl group or a lower alkyl group which may be substituted by a hydroxy group or a lower alkoxy group, or its pharmaceutically acceptable salt, and a process for preparing the same, an intermediate for synthesis of the same and a medicinal composition for bacterially infectious disease therapy containing the same.
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- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
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Compounds of the formula STR1 wherein R is hydrogen, R' is selected from the group consisting of alkenyl and alkynyl of 2 to 4 carbon atoms, A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base and the OR' group is in the syn position having antibiotic activity and process for their preparation.
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- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
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Compounds of the formula STR1 wherein R is selected from the group consisting of hydrogen and groups easily removable by acid hydrolysis or hydrogenolysis, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkenyl and alkynyl of 2 to 4 carbon atoms and groups easily removable by acid hydrolysis or hydrogenolysis, A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base with the proviso that when R' is a group easily removable by acid hydrolysis or hydrogenolysis, R is also and when R' is hydrogen, R also is hydrogen and the wavy line means the OR' group may be in either one of the two possible syn or anti positions having antibiotic activity and process for their preparation.
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