Silver(I) complexes with chromone-derived hydrazones: investigation on the antimicrobial and cytotoxic effects.

Complexes [Ag(HCrPh)2]NO3·2H2O (1) and [Ag(HCrpClPh)2]NO3 (2) were obtained with 3-formyl-6-methylchromone-phenyl hydrazone (HCrPh, HL1) and 3-formyl-6-methylchromone-para-chloro-phenyl hydrazone (HCrpClPh, HL2). Although the hydrazones were inactive, upon coordination to silver(I) antifungal activity significantly improved against several Candida strains. Complexes (1-2) revealed to be more active than silver nitrate, silver sulfadiazine and the reference drug nystatin against Candida parapsilosis. The cytotoxic activities of the hydrazones and their silver(I) complexes were evaluated in comparison with cisplatin on B16F10 (metastatic melanoma) and Melan-a (non-tumorigenic melanocyte) cells. The hydrazones showed low cytotoxicity against B16F10 cells, reducing only about 20% of cell viability at the concentration of 10 µM. Upon coordination to silver(I) the cytotoxic effect did not appreciably change in complex (1) while complex (2) proved to be as cytotoxic as cisplatin and much more cytotoxic than both the free ligand and silver nitrate at 1 µM. Both complexes (1) and (2) were less active than cisplatin on non-malignant Melan-a cells, indicating that these compounds might promote less damage on normal cells.

[Ag(L)NO3] Complexes with 2-Benzoylpyridine-Derived Hydrazones: Cytotoxic Activity and Interaction with Biomolecules.

Complexes [Ag(H2BzPh)NO3] (1), [Ag(H2BzpCH3Ph)NO3] (2), [Ag(H2BzpClPh)NO3] (3), and [Ag(H2BzpNO2Ph)NO3] (4) were synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its para-methyl-benzoylhydrazone (H2BzpCH3Ph), para-chloro-benzoylhydrazone (H2BzpClPh), and para-nitro-benzoylhydrazone (H2BzpNO2Ph) derivatives. Experimental data indicate that the nitrate ligand binds more strongly to the silver center through one of the oxygen atoms, whereas the second oxygen atom from nitrate and the hydrazone oxygen makes much weaker interactions with the metal. Dissociation of nitrate most probably occurs in solution and in biological media. Interestingly, theoretical calculations suggested that when dissociation of the nitrate takes place, all bond orders involving the metal and the atoms from the hydrazone ligand increase significantly, showing that the bonding of nitrate results in the weakening of all other interactions in the metal coordination sphere. Upon complexation of the hydrazones to silver(I), cytotoxicity against B16F10 metastatic murine melanoma cells increased in all cases. Complexes (1-3) proved to be more cytotoxic than cisplatin. All compounds were more cytotoxic to B16F10 cells than to nontumorigenic murine Melan-A melanocyte cells. Interestingly, the selectivity index (SI = IC50 non-malignant cells/IC50 tumor cells) of complex (1), SI = 23, was much higher than that of the parent hydrazone ligand, SI = 9.5. Studies on the interactions of complexes (1-3) with DNA suggested that although (1-3) interact with calf thymus DNA by an intercalative mode, direct covalent binding of silver(I) to DNA probably does not occur. Complexes (1-3) interact in vitro with human serum albumin indicating that these compounds could be transported by albumin.

Correction to [Ag(L)NO3] Complexes with 2-Benzoylpyridine-Derived Hydrazones: Cytotoxic Activity and Interaction with Biomolecules.

[This corrects the article DOI: 10.1021/acsomega.8b00533.].