Zn(II) complexes with pyridyl-based 1,3-selen/thiazolyl-hydrazones: A comparative study

The Zn(II) complexes [Zn(HLSe2)2](NO3)2 center dot CH3OH (2-NO3-Se ) and [Zn(HLSe3)2](NO3)2 center dot DMF (3-NO3- Se) with selenazolyl-hydrazone ligands 4-(4-methoxyphenyl)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3-selenazole (HLSe2) and 4-(4-methylphenyl)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3-selenazole (HLSe3) have been synthesized and characterized using singe crystal X-ray diffraction analysis. Antipro-liferative activities of 2-NO3-Se and 3-NO3-Se , the corresponding ligands and sulphur isosteres of the complexes and the ligands were determined on non-malignant HTR-8/SVneo extravillous trophoblast cell line and malignant JEG-3 and JAr choriocarcinoma cell lines. All Zn complexes exhibited cytotoxic ef-fect, comparable to that of a reference metal-based drug, cisplatin. The antioxidant activity of all com-pounds was determined in three antioxidant assays: ORAC (Oxygen Radical Absorbance Capacity), ABTS [(2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] and CERAC [Ce(IV)-based re-ducing capacity]. As a result of synergy between Zn(II) and selenazolyl-hydrazone ligands, the complexes 2-NO3-Se and 3-NO3-Se appeared to be more active than Trolox, which is not the case for their sulfur counterparts. In-silico calculations of ADME properties pointed that the compounds possess some of de-sirable Lipinski rule principles. Applied algorithms did not report the compounds as potential PAINS or covalent inhibitors, although due to high molecular weight none of the compounds represent a potential lead compound. Toxicity prediction of the compounds is performed using machine learning models. The complexation of the ligands most likely reduces their toxicity or reduces their negative metabolic effects. (c) 2023 Elsevier B.V. All rights reserved.