In vitro Assessment of the Cytotoxicity of Gallium(III) Complexes with Isoniazid-Derived Hydrazones: Effects on Clonogenic Survival of HCT-116 Cells

Publication date: Available online 16 August 2019Source: Inorganica Chimica ActaAuthor(s): Gisele dos S.S. Firmino, Stephanie C. André, Zandora Hastenreiter, Vanessa Karen Campos, Mostafa A.L. Abdel-Salam, Elaine M. de Souza-Fagundes, Josane A. LessaAbstractCancer cells have high iron demand to mediate their rapid proliferation. Aiming to obtain cytotoxic compounds with potential iron metabolism disturbance in malignant cells, [Ga(HAPIH)(APIH)](NO3)2⋅2H2O (1) and [Ga(HPAmIH)(PAmIH)](NO3)2⋅2H2O (2) were synthesized with the iron chelators 2-acetylpyridine- and 2-pyridineformamide isonicotinoyl hydrazone (HAPIH and HPAmIH, respectively) and gallium(III), an iron(III) mimetic. The hydrazones and their gallium(III) complexes were assayed for their action against HL−60 (leukemia), MCF−7 (breast cancer), HCT−116 (colorectal carcinoma) and PC3 (prostate cancer) tumor cell lines, as well as non-malignant Human Embryonic Kidney 293 (HEK−293) cells. HAPIH and its complex 1 were the most cytotoxic compounds, with HCT−116 being the most susceptible line (IC50 = 1.6 μM for HAPIH and 0.4 μM for complex 1). Moreover, the compounds proved to be at least 25-fold less toxic to HEK−293 than to the tumor cells. According to clonogenic survival assays, the relative number of colonies formed by HCT−116 cells was reduced by around 95% after pretreatment with HAPIH and 1 at their IC90 concentrations (18 μM and 4 μM, respectively). Both compounds were also able to inhibit ...
Source: Inorganica Chimica Acta - Category: Chemistry Source Type: research