Design and drug-like properties of new 5-methoxysalicylaldehyde based hydrazones with anti-breast cancer activity

Novel benzoylhydrazones were designed and synthesized by condensation of 5-methoxysalicylaldehyde and benzhydrazides with different substituents at 4th position. The structures of the new derivatives were confirmed by elemental and thermal analysis, mass, IR, H-1 NMR and C-13 NMR spectroscopy. The molecular properties of the compounds, important for drug pharmacokinetics and biodisposition in the human body, were assessed by the Lipinski's rule of five. In silico evaluation of the LogP value and the remaining parameters of drug similarity, as well as the topological polar surface area and absorption percentage, were used only as a first step in the study. The investigated 5-methoxyderivative hydrazones were further tested for in vitro cytotoxicity on three leukemic, two breast cancer and one non-tumor human cell lines using the MTT-dye reduction assay. The bioassay demonstrated that the compounds exhibited concentration-dependent antiproliferative activity at low micromolar concentrations against the used human cell lines. The solid tumor-derived breast cancer cell lines were generally more sensitive to the effects of the hydrazones with IC50 values ranging 0.91 mu M-12.07 mu M. The results confirm that all compounds are more potent than the standard drug Melphalan and have appropriate properties as potential anti-breast cancer drug candidates. (C) 2017 Faculty of Health and Social Sciences, University of South Bohemia in Ceske Budejovice. Published by Elsevier Sp. z o.o. All rights reserved.