A palladium(II) complex with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol: Synthesis, structural characterization, and in vitro and in silico biological activity studies.

The synthesis and characterization of the Pd(II) complex of the formula [Pd(L)2] 1 with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol (HL) as derived in situ via the condensation reaction of 5-chloro-salicylaldehyde and ethylamine was undertaken. The structure of 1 was verified by single-crystal X-ray crystallography. The ability of 1 to interact with calf-thymus (CT) DNA was studied by UV-vis and viscosity experiments, and its ability to displace ethidium bromide (EB) from the DNA-EB conjugate was revealed by fluorescence spectroscopy. It was found that intercalation is the most possible mode of interaction with CT DNA. Additionally, DNA electrophoretic mobility experiments showed that 1 interacts with the plasmid pBluescript SK(+) (pDNA) as proved by the formation of unusual mobility DNA bands and degradation of relaxed pDNA at concentration of 5 mM. The interaction of 1 with human (HSA) and bovine serum albumin (BSA) was monitored revealing its reversible binding to albumins. The complex showed noteworthy antimicrobial activity against one (Bacillus subtilis) of the five tested bacteria. In order to explain the described in vitro activity of the compound, we adopted molecular docking studies on the crystal structure of HSA, BSA, CT DNA and DNA-gyrase. Furthermore, in silico predictive tools have been employed to study the properties of the complex. The in silico studies are adopted on a multitude of proteins involved in cancer growth, as well as prediction of drug-induced changes of gene expression profile, protein- and mRNA-based prediction results, prediction of sites of metabolism, cytotoxicity for cancer cell lines, etc.

Palladium(II) complexes with salicylaldehyde ligands: Synthesis, characterization, structure, in vitro and in silico study of the interaction with calf-thymus DNA and albumins.

The synthesis and characterization of four palladium(II) complexes with substituted salicylaldehydes (X-saloH) having the general formula [Pd(X-salo)2] was undertaken. The complexes are formulated as [Pd(3-OCH3-salo)2] 1, [Pd(5-NO2-salo)2] 2, [Pd(5-Cl-salo)2] 3, and [Pd(5-Br-salo)2] 4. The structure of complex 1 was verified by single-crystal X-ray crystallography. Spectroscopic (UV-vis), and physicochemical (viscosity measurements) techniques were employed in order to study the binding of the complexes with calf-thymus (CT) DNA, while ethidium bromide (EB) displacement studies, performed by fluorescence emission spectroscopy, revealed the ability of the complexes to displace the DNA-bound EB. Intercalation is the most possible mode of interaction of the complexes with CT DNA. The interaction of the complexes with bovine (BSA) and human (HSA) serum albumin proteins was studied by fluorescence emission spectroscopy and the relatively high binding constants revealed the reversible binding of the complexes to the albumins. Molecular docking simulations on the crystal structure of HSA, BSA and CT DNA were employed in order to study in silico the ability of the studied complexes 1-4 to bind to these target macromolecules.

Interaction of dinuclear cadmium(II) 5-Cl-salicylaldehyde complexes with calf-thymus DNA.

Five dinuclear Cd(II) complexes with the anion of 5-Cl-salicylaldehyde (5-Cl-saloH) were synthesized in the absence or presence of the α-diimines: 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc) or 2,2'-dipyridylamine (dpamH) and characterized as [Cd(5-Cl-salo)2(CH3OH)]2 (1), [Cd(5-Cl-salo)2(bipy)]2 (2), [Cd(5-Cl-salo)2(phen)]2 (3), [Cd(5-Cl-salo)(neoc)(ONO2)]2 (4) and [Cd(5-Cl-salo)(dpamΗ)(ONO2)]2 (5). The complexes were characterized by spectroscopic techniques (IR, UV-vis, (1)H-NMR and (13)C-NMR), elemental analysis and molar conductivity measurements. The structures of four complexes (1-3 and 5) were determined by X-ray crystallography, providing all three possible coordination modes of the ligand 5-Cl-salicylaldehyde, i.e. bidentate or tridentate chelating and/or bridging mode. The complexes bind to calf-thymus (CT) DNA mainly by intercalation, as concluded by the viscosity measurements and present relatively high DNA-binding constants. The complexes exhibit significant ability to displace ethidium bromide (EB) from the EB-DNA complex, thus indirectly proving the intercalation as the most possible binding mode to CT DNA.

Synthesis of novel thiopurine pyranonucleosides: evaluation of their bioactivity.

We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a-e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a-e and thioguanine 4a-e nucleosides, while their N-7 substituted congeners 10a-e and 7a-e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a-e, 5a-e, 8a-e, and 11a-e were evaluated for their cytostatic activity in three different tumor cell proliferative assays.

Synthesis, characterization, thermal and DNA-binding properties of new zinc complexes with 2-hydroxyphenones.

The neutral mononuclear zinc complexes with 2-hydroxyphenones (ketoH) having the formula [Zn(keto)2(H2O)2] and [Zn(keto)2(enR)], where enR stands for a N,N'-donor heterocyclic ligand such as 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2'-dipyridylamine (dpamH), have been synthesized and characterized by IR, UV and (1)H NMR spectroscopies. The 2-hydroxyphenones are chelated to the metal ion through the phenolate and carbonyl oxygen atoms. The crystal structures of [bis(2-hydroxy-4-methoxy-benzophenone)(2,2'-bipyridine)zinc(II)] dimethanol solvate and [bis(2-hydroxy-benzophenone)(2,2'-bipyridine)zinc(II)] dimethanol solvate have been determined by X-ray crystallography. The thermal stability of the zinc complexes has been investigated by simultaneous TG/DTG-DTA technique. The ability of the complexes to bind to calf-thymus DNA (CT DNA) has been studied by UV-absorption and fluorescence emission spectroscopy as well as viscosity measurements. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the corresponding binding constants to DNA have been calculated and evaluated. The complexes most probably bind to CT DNA via intercalation as concluded by studying the viscosity of a DNA solution in the presence of the complexes. Competitive studies with ethidium bromide (EB) have shown that the reported complexes can displace the DNA-bound EB, suggesting strong competition with EB for the intercalation site.

Zinc complexes of salicylaldehydes: synthesis, characterization and DNA-binding properties.

The neutral mononuclear zinc complexes with substituted salicylaldehydes, in the absence or presence of a nitrogen donor heterocyclic ligand 2,2'-bipyridine or 1,10-phenanthroline or 2,2'-dipyridylamine, have been synthesized and characterized by IR, UV and NMR spectroscopies. The experimental data suggest that salicylaldehyde is on deprotonated mode acting as a bidentate ligand coordinated to the metal ion through the phenolato and one aldehydo oxygen atoms. The crystal structures of bis(5-nitro-salicyladehydato)(2,2'-dipyridylamine)zinc(II), bis(5-chloro-salicylaldehydato)(2,2'-bipyridine)zinc(II) monohydrate and bis(5-bromo-salicyladehydato)bis(methanol)zinc(II) have been determined with X-ray crystallography. The ability of the complexes to bind to calf-thymus DNA (CT DNA) has been studied by UV and fluorescence spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA. The calculated binding constants of the complexes to DNA reveal tight binding to DNA. The complexes can probably bind to CT DNA via intercalation as concluded by studying the viscosity of a DNA solution in the presence of the complexes. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB suggesting strong competition with EB for the intercalation site of DNA.

Synthesis and biological evaluation of 3'-C-ethynyl and 3'-C-(1,4-disubstituted-1,2,3-triazolo) double-headed pyranonucleosides.

A novel series of 3'-C-ethynyl and 3'-C-(1,4-disubstituted-1,2,3-triazolo) double-headed pyranonucleosides has been designed and synthesized. Reaction of 3-keto glucoside 1 with ethynyl magnesium bromide gave the desired precursor 3-C-ethynyl-1,2:5,6-di-O-isopropylidene-α-D-allofuranose (2). Hydrolysis followed by acetylation led to the 1,2,4,6-tetra-O-acetyl-3-C-ethynyl-ß-D-allopyranose (3). Compound 3 was condensed with silylated 5-fluorouracil, uracil, thymine, N4-benzoylcytosine and N6-benzoyladenine, respectively and deacetylated to afford the target 1-(3'-C-ethynyl-ß-D-allopyranosyl)nucleosides 5a-c,f,g. Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction was utilized to couple the 3'-C-ethynyl pyranonucleoside derivatives with azidoethyl adenine, 5-fluorouracil and thymine, respectively to afford novel triazole double-headed nucleoside analogs 8a-h. 3'-C-Ethynyl pyranonucleosides and the new double-headed analogues were evaluated for their antiviral and cytostatic activities. Although none of the compounds showed pronounced cytostatic activity and were devoid of a significant antiviral potential, the double-headed nucleoside derivatives 8a, 8c and 8e showed a moderate cytostatic activity against human cervix carcinoma HeLa cells which may be the basis for the synthesis of analogous derivatives with improved cytostatic potential.

Synthesis of a protected trihydroxyindolizidine 3-carboxylate via a hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to a D-ribose-derived exo-glycal.

A protected trihydroxyindolizidine 3-carboxylate was prepared by a 6-endo epoxide cleavage, which in turn was intermediately formed from the hetero-Diels-Alder adduct of ethyl 2-nitrosoacrylate to a D-ribose-derived exo-glycal.

Synthesis of C-glycosylated amino acids by hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to exo-glycals.

C-Glycoamino acids bearing a variety of sugar moieties were prepared by the hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to exo-glycals. The reaction proceeds smoothly to yield spirocyclic oxazines that can be converted into useful products by several hydrogenolytic techniques.

Application of chiral cyclic nitrones to the diastereoselective synthesis of bicyclic isoxazolidine nucleoside analogues.

New bicyclic isoxazolidine nucleoside analogues are synthesized through 1,3-dipolar cycloaddition of enantiopure cyclic nitrones to appropriate vinyl nucleobases. The reactions are diastereoselective, giving as the main or the sole product the exo-Re cycloadducts. The diastereoselectivity depends on both the kind of the base and the substitution pattern of the nitrone.

Synthesis and characterization of nonconventional surfactants of aromatic amino acid-glycerol ethers: effect of the amino acid moiety on the orientation and surface properties of these soap-type amphiphiles.

The synthesis, characterization, and surface properties of soap-type amphiphiles comprising alkyl chains of 10-16 carbon atoms linked through an ether group to a glycerol-amino acid hydrophilic head group is described. The surface properties of members of this series derived from histidine and tyrosine were compared with those of phenylalanine and tryptophan derivatives described previously and with those of conventional soaps. In all cases, the amino acid derivatives showed superior surface properties, and an interesting differentiation was discovered regarding the orientation of tryptophan derivatives.

Labeling of organic biomolecules with ethynylferrocene.

The Sonogashira coupling reaction of ethynylferrocene with adenine, uracil, tyrosine and steroid derivatives was studied; with the exception of tyrosine it was proved to be a good route for the attachment of ferrocene to these representative biomolecules. In addition the transformation of alkynyl uracil to furanopyrimidone derivatives was investigated and the formation of the furanopyrimidone ring was confirmed by an X-ray crystallographic analysis carried out on product 16.