Homo- and heterometallic complexes of Zn(ii), {Zn(ii)Au(i)}, and {Zn(ii)Ag(i)} with pentadentate Schiff base ligands as promising anticancer agents

Two families of homo- and heterometallic complexes, [Zn2L1(μ-OH)(H2O)2](ClO4)2, [Zn2L2(μ-OH)(H2O)2](ClO4)2, [Zn2L3(μ-OH)(H2O)2](ClO4)2, 1∞[{L1Zn2(μ-OH)}{μ-[Ag(CN)2]}](ClO4), [{L1Zn2(μ-OH)}2{μ-[Au(CN)2]}{[Au(CN)2]2}](ClO4)·H2O, 1∞[{L2Zn2(μ3-OH)}2(H2O){μ-[Ag(CN)2]}](ClO4)3·THF·0.5MeOH, 1∞[{L2Zn2(μ3-OH)}2(H2O){μ-[Au(CN)2]}](ClO4)3·THF·H2O, and 1∞[{L3Zn2(μ-OH)}{μ-[Ag(CN)2]}][Ag(CN)2]·H2O, respectively, have been synthesized and characterized. The Schiff bases used as ligands were obtained by condensation reactions of 2,6-diformyl-p-cresol with N,N-dimethyl-ethylenediamine (HL1), 2-aminomethyl-pyridine (HL2), and 2-aminoethyl-pyridine (HL3), respectively. The cytotoxic/cytostatic and genotoxic effects in cultured human MCF-7 (luminal type A breast cancer), MDA-MB-231 (triple negative breast cancer), HeLa (cervical carcinoma), and Lep-3 (non-tumor embryonal fibroblastoid cells) were studied. The investigations were performed by thiazolyl blue tetrazolium bromide test (MTT test), neutral red uptake cytotoxicity assay, crystal violet staining, hematoxylin and eosin staining, double staining with acridine orange and propidium iodide, AnnexinV/FITC, and Comet assay in short-term experiments (24-72 h, with monolayer cell cultures) as well as by 3D colony-forming method in long-term experiments (28 days, with 3D cancer cell colonies). The results obtained revealed that: (i) applied at a concentration range of 0.1-100 μg mL-1, the compounds investigated decrease in a time- and concentration-dependent manner the viability and/or proliferation of the treated cells; (ii) complexes of {Zn(II)Au(I)} show relatively higher cytotoxic/genotoxic activity and antitumor potential as compared to {Zn(II)Ag(I)}; (iii) some of the complexes demonstrate more pronounced cytotoxic potential than commercially available antitumor agents cisplatin, oxaliplatin, and epirubicin.