SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF METAL COMPLEXES DERIVED FROM 2-(PHENYLAMINO)ACETOHYDRAZIDE LIGAND

Fathy A. El-Saied*, Tarek A. Salem, Bishoy Y. El-Aarag, Manar A. Hashim

ABSTRACT

Metal complexes of the ligand, 2-(phenylamino)acetohydrazide (HL) with Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Cr(III) and Fe(III) ions were synthesized and characterized using elemental, spectral (IR, UV- VIS), and thermal analyses (TGA) as well as magnetic moment and molar conductance measurements. The ligand in the obtained solid complexes coordinates as a bi-dentate either as a neutral via the amino group nitrogen and carbonyl oxygen atoms or anilino NH or as a monobasic via the amino group nitrogen atom and enolic (C-O) oxygen atom in the enolimine-tautomeric form. The cytotoxic effect of these complexes was estimated against Hep-G2 cancer cell lines. Also, the in-vivo model of hepatic fibrosis was induced by the intraperitoneal (i.p) injection of carbon tetrachloride (CCl4) in mice and the possible antifibrotic activities of these complexes were estimated. Moreover, liver function, histopathological examination of liver, and expression of caspase 3 in liver tissues were assayed. Results revealed that all the newly synthesized complexes exhibited cytotoxic effect on Hep-G2 cell lines. Also, administration of Cu(II) complexes to the CCl4-intoxicated mice led to improvement the hepatic function and liver histology. Furthermore, the treatment of CCl4-intoxicated with ligand and copper complexes led to a marked decrease in the caspase 3 expression in nucleus and cytoplasm of hepatic cells. In conclusion, Cu(II) complexes of hydrazide derivatives, specially Cu(II) perchlorate, showed anticancer and antifibrotic activities higher than the ligand. The potential activity of the tested complexes might be due to their cytotoxicity and ability to reduce the expression of apoptotic gene caspase-3 that helps in the repairing of liver cells.

Keywords: Cytotoxic activity; Hep-G2; Fibrosis; Caspase-3; Hydrazide ligand; Metal complexes.