Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver

Synthesis, characterization and crystal structure of butyl N-(3-chloropropyl)-(2S)-alaninate hydrochloride

The synthesis of butyl N-(3-chloropropyl)-(2S)-alaninate hydrochloride is reported here. The compound was characterized by elemental analysis, infrared, and 1H- and 13C-NMR spectroscopy. The structure of butyl N-(3- chloropropyl)-(2S)-alaninate hydrochloride was confirmed by single-crystal X-ray analysis.The authors are grateful for the financial support to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Projects No. 172016 and 172035).Peer Reviewe

Stereospecific ligands and their complexes. VI. The crystal structure of (S,S)-ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S)-H2eddp•HCl

(S,S)-Ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S)-H2eddp·HCl, was prepared and its crystal structure determined. The compound was characterized by infrared and 1H- and 13C-NMR spectroscopy. It forms P1 in the space group of a triclinic crystal system with a = 5.3902(2) Å, b = 5.8967(2) Å, c = 10.3319(2) Å, a = 99.625(2)°, b = 91.645(2)°, g = 109.995(2)° and Z = 1

Synthesis and high in vitro cytotoxicity of some (S,S)-ethylenediamine-N,N’-di-2-propanoate dihydrochloride esters

Novel (S,S)-R2eddip ester, O,O’-diisoamyl-(S,S)-ethylenediamine-N,N’-di-2-propanoate dihydrochloride, 1, was synthesized and characterized by IR, 1H and 13C NMR spectroscopy, mass spectroscopy and elemental analysis.In vitro antitumor action of 1, and two more R2eddip esters, O,O’-dialkyl-(S,S)-ethylenediamine-N,N’-di-2-propanoate dihydrochlorides, obtained before, (alkyl = n-Bu, n-Pe; 2 and 3, respectively), was determined against cervix adenocarcinoma (HeLa), human melanoma (Fem-x), human chronic myelogenous leukemia (K562) cells, and a non-cancerous cell line human embryonic lung fibroblast (MRC-5), using MTT assay. Esters 1-3 showed higher cytotoxicity and better selectivity in comparison to cisplatin, used as reference compound. The highest activityis expressed by1,with IC50(Fem-x)value1.51 ± 0.09 µM. [Projekat Ministarstva nauke republike Srbije, br. 172035 i br. 175011

Synthesis, characterization and antimicrobial activity of novel platinum(IV) and palladium(II) complexes with meso-1,2-diphenyl-ethylenediamine-N,N -di-3-propanoic acid - Crystal structure of H-2-1,2-dpheddp center dot 2HCl center dot H2O

In the reaction of meso-1,2-diphenyl-ethylenediamine (1,2-dphen) with neutralized 3-chlor-propanoic acid, the new linear tetradentate edda-like ligand (edda = ethylenediamine-N,N-diacetic ion) meso-1, 2-diphenyl-ethylenediamine-N,N-di-3-propanoic acid dihydrochloride monohydrate (H-2-1,2-dpheddp center dot 2HCl center dot H2O) was prepared. The corresponding platinum(IV) complex, s-cis-dichlorido-(meso-1,2-diphenyl-ethylenediamine-N,N-di-3-propanoate)-platinum(IV) ([PtCl2(1,2-dpheddp)]) was synthesized by heating potassium-hexachloridoplatinate(IV) and H-2-1,2-dpheddp center dot 2HCl center dot H2O on steam bath for 12 h with neutralization by means of lithium-hydroxide. The palladium(II) complex, cis-dichlorido-(meso-1,2diphenyl-ethylenediamine-N,N-di-3-propanoate)-palladium(II) (IPdCl2(1,2-dpheddp)]) was obtained in the similar way using potassium-tetrachloridopalladate(II), H-2-1,2-dpheddp-2HCl center dot H2O and lithium-hydroxide. The compounds were characterized by elemental analysis and infrared spectroscopy. The spectroscopically predicted structure of the synthesized tetradentate ligand was confirmed by X-ray analysis of the H-2-1,2-dpheddp.2HCl center dot H2O. Antimicrobial activity of the ligand and corresponding palladium(II) and platinum(IV) complexes is investigated against 25 species of microorganisms. Testing is preformed by microdilution method and minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) have been determined. The difference between antimicrobial activity of the ligand and corresponding platinum(IV) and palladium(II) complex is noticed and, in general, palladium(II) complex was the most active. (C) 2012 Elsevier B.V. All rights reserved

Stereospecific ligands and their complexes. Part XV. Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with some esters of ethylenediamine-N,N'N'-di-S,S-(2,2''-dibenzyl)acetic acid. Crystal structure of O,O''-dipropyl-ethylenedi

The synthesis of ethylenediamine-N,N-di-S,S-(2,2-dibenzyl)acetic acid (H-2-S,S-eddba) and its ethyl-, propyl-, butyl-esters (R-2-S,S-eddba) are reported here. The esters were used for synthesis of the corresponding platinum(IV) complexes, [PtCl4(R-2-S,S-eddba)]. The compounds were characterized by elemental analysis, infrared, H-1 and C-13 NMR spectroscopy. The structure of propyl ester of H-2-S,S-eddba was confirmed by single-crystal X-ray analysis. All [PtCl4(R-2-S,S-eddba)] complexes displayed significantly higher in vitro cytotoxicity in comparison to cisplatin. (C) 2013 Published by Elsevier B.V

Interactions of binuclear copper(II) complexes with S-substituted thiosalicylate derivatives with some relevant biomolecules

Interactions of copper(II) complexes which contain S-alkyl derivatives of thiosalicylic acid (alkyl = methyl, ethyl, propyl and butyl; aryl = benzyl), marked as 1–5, with guanosine-5′-monophosphate (5′-GMP) and calf thymus DNA (CT-DNA) were studied. Kinetics of substitution reactions of 1–5 with 5′-GMP and CT-DNA were investigated under pseudo-first-order conditions at 310 K and pH = 7.2 in 25 mM Hepes buffer using stopped-flow method. All complexes have high affinity toward studied bio-molecules. Additionally, interactions with CT-DNA were followed by absorption spectroscopy and fluorescence quenching measurements. The results indicate that complexes bind to DNA exhibiting high binding constants (Kb = 104 M−1). During the examination of competitive reactions with ethidium bromide (EB), results showed that complexes can replace EB-bound DNA. In addition, a new crystal structure of the binuclear Cu(II) complex with S-substituted thiosalicylate derivative has been reported. In the present series of Cu(II) complexes the crystal structure is the first example of a complex comprising an S-aryl derivative of thiosalicylate ligand. Through comparative study of structural properties of six molecules from four crystal structures we examined the structural variations, potentially important for biological activity of these complexes. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group