فرم جدید از تیوسمی کاربازون های محلول در اب و کمپلکس های مس آنها به عنوان ترکیبات بالقوه ضد سرطانی

عنوان انگليسی

New series of water-soluble thiosemicarbazones and their copper (II) complexes as potentially promising anticancer compounds

خلاصه انگلیسی

New water soluble thiosemicarbazone ligands, namely 3-(3-{[(aminocarbonothioyl) hydrazono]methyl}-4- hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L1Cl), 3-[4-hydroxy-3-({[(methylamino) carbonothioyl]hydrazono}methyl)benzyl]-1-methyl-1H-imidazol-3-ium chloride (H2L2Cl) and 3-(3- {[(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L3Cl) were synthesized through 1:1 condensation reaction of thiosemicarbazide derivatives with 3-(3-formyl-4- hydroxybenzyl)-1-methyl-1H-imidazole-3-ium chloride (SalimiCl) and characterized by elemental analysis and spectroscopic methods (UV–Vis, 1 H NMR, FTIR). Single crystals of H2L1Cl and H2L2Cl were prepared for crystallographic analysis, which showed similar X-ray structures for both ligands with chiral P212121 space group. The ligands were used for synthesis of the following copper(II) complexes: [Cu(HL1)Cl]Cl, [Cu(HL2)Cl]Cl·H2O, and [Cu(HL3)Cl]Cl. All complexes were characterized by physico-chemical and spectroscopic methods. The X-ray structure of [Cu(HL1)Cl]Cl was orthorhombic with Pcba space group while [Cu(HL2)Cl]Cl·H2O was triclinic with Pī space group. Both complexes were mononuclear, with tridentate ligands in a thione form. All of the studied compounds showed good solubility and stability in water. The measurement of the molar conductance showed the release of Cl− into solution and substitution of water instead of the coordinated chloride. Among the studied complexes, only [Cu(HL3)Cl]Cl shows a quasi-reversible redox behavior with its reduction and oxidation peak potentials separated by a value of about 0.120 V (Epc = −0.310 V and Epa = −0.190 V) indicating onestep and one-electron transfer for CuII/CuI redox couple. The cytotoxic effect of the compounds was measured using the MTT assay on MCF-7 and K562 cell lines and the results showed that [Cu(HL3)Cl]Cl and H2L3Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the MCF-7 cells showed the apoptosis cell death after treating with the H2L3Cl and [Cu(HL3)Cl]Cl. Also studies of cell cycles confirmed the cell cycle arrest in G2 phase for H2L3Cl and [Cu(HL3)Cl]Cl.

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