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J Inorg Biochem ; 223: 111549, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34315119

RESUMO

Four new transition metal complexes, [M(PPh3)(L)].CH3OH (M = Ni(II) (1), Pd(II) (2)) [Pt (PPh3)2(HL)]Cl (3) and [Ru(CO)(PPh3)2(L)] (4) (H2L = 2,4-dihydroxybenzaldehyde-S-methyldithiocarbazate, PPh3 = triphenylphosphine) have been synthesized and characterized by elemental analyses (C, H, N), FTIR, NMR (1H, 31P), ESI-MS and UV-visible spectroscopy. The molecular structure of (1) and (2) complexes was confirmed by single-crystal X-ray crystallography. It showed a distorted square planar geometry for both complexes around the metal center, and the H2L adopt a bi-negative tridentate chelating mode. The interaction with biomolecules viz., calf thymus DNA (ct DNA), yeast RNA (tRNA), and BSA (bovine serum albumin) was examined by both UV-visible and fluorescence spectroscopies. The antioxidant activity of all compounds is discussed on basis of DPPH• (2,2-diphenyl-1-picrylhydrazyl) scavenging activity and showed better antioxidant activity for complexes compared to the ligand. The in vitro cytotoxicity of the compounds was tested on human (breast cancer (MCF7), colon cancer (HCT116), liver cancer (HepG2), and normal lung fibroblast (WI38)) cell lines, showing that complex (1) the most potent against MCF7 and complex (4) against HCT116 cell lines based on IC50 and selective indices (SI) values. So, both complexes were chosen for further studies such as DNA fragmentation, cell apoptosis, and cell cycle analyses. Complex (1) induced MCF7 cell death by cellular apoptosis and arrest cells at S phase. Complex (4) induced HCT116 cell death predominantly by cellular necrosis and arrested cell division at G2/M phase due to DNA damage.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Sequestradores de Radicais Livres/farmacologia , Hidrazinas/farmacologia , Fosfinas/farmacologia , Tiocarbamatos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , DNA/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/síntese química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Hidrazinas/síntese química , Hidrazinas/metabolismo , Metais Pesados/química , Fosfinas/síntese química , Fosfinas/metabolismo , Ligação Proteica , RNA de Transferência/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Soroalbumina Bovina/metabolismo , Tiocarbamatos/síntese química , Tiocarbamatos/metabolismo , Leveduras/química
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