Evaluation of the antitumor activity of a series of the pincer-type metallocomplexes produced from isonicotinohydrazide derivative

Abstract

In this work we report on the antitumor properties of a series of pincer-type metallocomplexes [Hg₂(HL-keto)Cl₄]_n (1), [Hg(HL-keto)I₂] (2) and [Mn(HL-zwitterion)Cl₂]∙MeOH (3∙MeOH), derived from N'-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL) and corresponding metal salts. The Hg(II) and Mn(II) salts are chelated by the keto (HL-keto) or zwitterionic (HL-zwitterion) form of HL, respectively. The cytotoxic effects of these compounds have been accessed against lung adenocarcinoma (A549) and hepatocellular carcinoma (HepG2 and Huh7) cell lines. Complexes 1 and 2 were found to be most efficient against the cell line Huh7 with IC₅₀ value of 2.56 and 9.90 μM, respectively, while they exhibit moderate activity towards cell lines A549 and HepG2, as evidenced from IC₅₀ values in the range 27.98-56.99 μM. Complex 3∙MeOH is less efficient towards all the three cell lines with relatively high IC₅₀ values. The mechanisms of the metallocomplexes killing the aforementioned cells were elucidated by flow cytometry, colony formation and polymerase chain reaction (PCR) analysis of apoptosis related expression of the genes. The results of the cytotoxic effects and antitumor activity on different cell lines are affected by the metal nature and the presence of the coordinated halide.

Keywords: Antitumor activity; Apoptosis; Crystal structure; Cytotoxicity; Isonicotinohydrazone; Pincer type complexes.