Interaction of Arylidenechromanone/Flavanone Derivatives with Biological Macromolecules Studied as Human Serum Albumin Binding, Cytotoxic Effect, Biocompatibility Towards Red Blood Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2018-12, Vol.23 (12), p.3172
• Main Authors: Adamus-Grabicka, Angelika A, Markowicz-Piasecka, Magdalena, Ponczek, Michał B, Kusz, Joachim, Małecka, Magdalena, Krajewska, Urszula, Budzisz, Elzbieta
• Format: Article
• Language: English
• Subjects: Albumin; Asymmetry; benzoflavanone/chromanone derivatives; Binding; Biocompatibility; Cancer; Cell Line, Tumor; Cell Survival - drug effects; crystal structure; Crystallography, X-Ray; cytotoxic effect; Cytotoxicity; Erythrocytes; Erythrocytes - drug effects; erythrotoxicity; Flavanones - chemistry; Flavanones - pharmacology; Flavonoids; Hemolysis - drug effects; Human serum albumin; Humans; Hydrocarbons; Hydrogen Bonding; Hydrogen bonds; Informatics; Infrared analysis; Leukemia; Macromolecular Substances - chemical synthesis; Macromolecular Substances - chemistry; Macromolecular Substances - metabolism; Macromolecules; Melanoma; Models, Molecular; Molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; NMR; Nuclear magnetic resonance; Protein Binding; Proteins; Serum albumin; Serum Albumin, Human - chemistry; Serum Albumin, Human - metabolism; Signal transduction; Structure-Activity Relationship; synthesis; Tumor cell lines; X-ray diffraction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23123172

The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3arylideneflavanone (2) on HL-60 and NALM-6 cell lines (two human leukemia cell lines) and a WM-115 melanoma cell line. Both compounds exhibited high cytotoxic activity with higher cytotoxicity exerted by compound 2, for which IC values below 10 µM were found for each cell line. For compound 1, the IC values were higher than 10 µM for HL-60 and WM-115 cell lines, but IC < 10 µM was found for the NALM-6 cell line. Both compounds, at the concentrations close to IC (concentration range: 5⁻24 µM/L for compound 1 and 6⁻10 µM/L for compound 2), are not toxic towards red blood cells. The synthesized compounds were characterized using spectroscopic methods ¹H- and C-NMR, IR, MS, elemental analysis, and X-ray diffraction. The lipophilicity of both synthesized compounds was determined using an RP-TLC method and the logP values found were compared with the theoretical ones taken from the Molinspiration Cheminformatics (miLogP) software package. The mode of binding of both compounds to human serum albumin was assessed using molecular docking methods.