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

Angelika A Adamus-Grabicka,Magdalena Małecka,Michał B Ponczek,Elzbieta Budzisz,Magdalena Markowicz-Piasecka,Joachim Kusz,Urszula Krajewska

doi:10.3390/molecules23123172

Abstract

The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3-arylideneflavanone (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 IC50 values below 10 µM were found for each cell line. For compound 1, the IC50 values were higher than 10 µM for HL-60 and WM-115 cell lines, but IC50 < 10 µM was found for the NALM-6 cell line. Both compounds, at the concentrations close to IC50 (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 13C-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.

Highlights

Flavonoids constitute a large group of natural and synthetic polyphenolic compounds with a wide range of antioxidant, anti-allergic, anti-inflammatory, anti-microbial, anti-coagulant, anti-cholesterol, or anti-cancer activities
The cytotoxic effects of E and Z-isomers of benzylideneflavanone are compared in a previous paper [11]
The current paper compares the cytotoxicity of chromanone and flavanone derivatives. (E)-3-(4-N,N-diethylaminobenzylidene)chroman-4-one (1) and (E)-3-(4-N,N-diethylaminobenzylidene)-2-phenylchroman-4-one (2) synthesized, as described previously [14] (Scheme 1)

Summary

Introduction

Flavonoids constitute a large group of natural and synthetic polyphenolic compounds with a wide range of antioxidant, anti-allergic, anti-inflammatory, anti-microbial, anti-coagulant, anti-cholesterol, or anti-cancer activities. These properties often depend on unknown structure-related interactions with nucleic acids and proteins [1,2]. Molecules 2018, 23, 3172 apoptosis, as well as the processes of inflammation, angiogenesis, and metastasis [3] Due to their multidirectional mechanisms of action, flavonoids are promising candidates for novel anti-cancer agents and are being extensively investigated for the treatment of neoplastic diseases [3,4,5]. It was found that, in vivo, quercetin exerts a chemo-preventive effect on prostate cancer (reduces the cell viability) by downregulating the activity of pro-proliferative and anti-apoptotic proteins [6]

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