Novel binuclear copper(II) complexes with sulfanylpyrazole ligands: synthesis, crystal structure, fungicidal, cytostatic, and cytotoxic activity.

New binuclear copper(II) [Cu(II)] tetraligand complexes (six examples) with sulfanylpyrazole ligands were synthesized. Electron spin resonance (ESR) studies have shown that in solution the complexes are transformed to the mononuclear one. Fungicidal properties against Candida albicans were found for the Cu complexes with benzyl and phenyl substituents. An in vitro evaluation of the cytotoxic properties of Cu chelates against HEK293, Jurkat, MCF-7, and THP-1 cells identified the Cu complex with the cyclohexylsulfanyl substituent in the pyrazole core as the lead compound, whereas the Cu complex without a sulfur atom in the pyrazole ligand had virtually no cytotoxic or fungicidal activity. The lead Cu(II) complex was more active than cisplatin. Effect of the S-containing Cu complex on apoptosis and cell cycle distribution has been investigated as well.

Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.

1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N,N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N,N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.

Synthesis, crystal structure, and in vitro evaluation of the anticancer activity of new Pt (Pd) complexes with 1-[(dimethylamino)methyl]-2-naphthol ligand.

The synthesis of new Pt(II) and Pd(II) complexes with 1-aminomethyl-2-naphtol ligands has been first performed. The adducts of [PtCl4]2- and [PdCl4]2- anions with the 1-aminomethyl-2-naphtol NH cation were synthesized. The structure for four Pt (Pd)-containing compounds was investigated using X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat and K562 human leukemia cells, lymphoma U937cells, A2780 and the cisplatin-resistant A2780cis lines of human ovarian cancer, and normal fibroblasts. Study of induction of apoptosis and the effect of new palladium and platinum complexes on the cell cycle was carried out. The cells showed a higher sensitivity to Pt(II) compounds than to Pd(II) ones. All the synthesized metal complexes show much more antitumor activity compared with a platinum-containing cisplatin drug.

2-Amino-3,5-dicarbonitrile-6-sulfanylpyridines: synthesis and multiple biological activity - a review.

This review integrates the published data of the last decade (from 2010 to 2020) on the synthesis of the 2-amino-3,5-dicarbonitrile-6-sulfanylpyridine scaffold, the derivatives of which are widely used in the synthesis of biologically active compounds. Currently, no systematic accounts of synthetic routes towards this class of heterocyclic compounds can be found in the literature. The present-day trends in the catalytic synthesis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines are considered using pseudo-four-component reaction (pseudo-4CR) by condensation of malononitrile molecules with thiols and aldehydes, and alternative three-component (3CR) condensations of malononitrile with 2-arylidenemalononitrile and S-nucleophiles.

Metal-free multicomponent synthesis of novel macrocyclic tetrathiadienes with cyano and amino groups.

The first synthesis of 5,12-diamino-7,14-bis(aryl)-1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitriles was performed as a multicomponent macroheterocyclization of malononitrile, aryl aldehydes, and 1,2-ethanedithiol in the presence of a catalytic amount of triethylamine in ethanol. The structures of the obtained macroheterocycles were confirmed by spectral methods, X-ray diffraction, and MALDI TOF mass spectrometry.

Synthesis of new N,N'-Pd(Pt) complexes based on sulfanyl pyrazoles, and investigation of their in vitro anticancer activity.

The synthesis of new N,N'-mononuclear bi-ligand Pd(ii) and tri-ligand Pt(ii)complexes bearing sulfanyl(phenyl, benzyl, cyclohexyl, 4-hydroxyphenyl)3,5-dimethyl-1H-pyrazole ligands has been carried out. The obtained compounds were studied for apoptosis-inducing activity and effect on the cell cycle for Jurkat, K562, and U937 neoplastic cell cultures and conditionally normal human embryonic kidney HEK293 cells. The cells showed the highest sensitivity to platinum and palladium complexes in comparison with ligands and cisplatin. The cytotoxic properties are enhanced for compounds with cyclohexyl substituents at the S-atom in sulfanyl pyrazoles and complexes.

A green synthesis in water of novel (1,5,3-dithiazepan-3-yl)alkanoic acids by the multicomponent reaction of amino acids, CH2O, and 1,2-ethanedithiol.

A library of new (1,5,3-dithiazepan-3-yl)alkanoic acids was prepared by the multicomponent cyclocondensation of amino acids, formaldehyde, and 1,2-ethanedithiol in water at room temperature for 1 to 5 h in high yields. This green procedure offers several advantages such as an operational simplicity, no catalyst, and no production of hazardous materials.

Stereoelectronic effects in N-C-S and N-N-C systems: experimental and ab initio AIM study.

The energy of stereoelectronic interactions in N-C-S and N-N-C systems in tetrahydro[1,3,4]thiadiazolo[3,4- c][1,3,4]thiadiazole was estimated by means of R. W. Bader's quantum theory of "atoms in molecules" (AIM) and natural bond orbital analysis (NBO). The results were compared with those obtained by analysis of rho( r) derived from high-resolution X-ray diffraction data. The analysis of the data obtained allowed one to find a correlation between geometric characteristics of the stereoelectronic interactions, NBO mixing energies and the AIM properties of atoms. Significant variations of nitrogen atom atomic basin populations in different conformers were explained by sterical interactions between their electron lone pairs.