J Appl Biomed 15:233-240, 2017 | DOI: 10.1016/j.jab.2017.04.004

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

Boryana Nikolova-Mladenova^a,*, Georgi Momekov^b, Darvin Ivanov^a, Adriana Bakalova^a

^a Department of Chemistry, Faculty of Pharmacy, Medical University Sofia, Sofia, Bulgaria

^b Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University Sofia, Sofia, Bulgaria

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, ¹H NMR and ¹³C 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 μM-12.07 μM. 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.

Keywords: 5-methoxysalicylaldehyde; Salicylaldehyde benzoylhydrazone; Lipophilicity; Antiproliferative activity; Anti-breast cancer activity

Received: August 18, 2016; Revised: April 12, 2017; Accepted: April 25, 2017; Published: July 1, 2017  Show citation