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

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.

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

“…Following on from a previous paper [10], the present study broadens our studies of the reactivity of 3-arylideneflavanones and 3-arylidenechromanone with diazomethane on a larger number of compounds containing various benzylidene substituents. The formation of spiro-compounds as a result of attack by a nucleophilic reagent on the carbon of the 3-arylideneflavanone most probably depends on the degree of electropositivity of the carbon; this would govern reactions with the various resonance structures of diazomethane [9].…”

“…Two structures, benzylideneflavanone and benzylidenechromanone substituted with diethylamine group, have been examined previously in a study that compared the exacytotoxic activity of the two compounds and checked whether they destroy erythrocyte membranes [10]. Encouraged by these positive results, the present manuscript examines the relationship between the biological activity of the tested compounds and their chemical structure: for this purpose ten 3-arylidenechromanone analogues with a ∆ 1 -pyrazoline ring were synthesized and their physicochemical characteristics, together with their cytotoxicity, determined.…”

“…It is also worth mentioning that in further studies we also used two additional compounds: (E)-3-(4-N,N-diethylaminobenzylidene)chroman-4-one (12) and (E)-3-(4-N,N-diethylaminobenzylidene)-2-phenylchroman-4-one (11). Their synthesis, structure and promising antiproliferative properties against cancer cells (HL-60, NALM-6 and WM-115) have been described previously [10]. Both compounds showed high cytotoxic activity against the HL-60 cell line: 11.76 µM 12 and 8.36 µM 11.…”

“…In addition to the compounds shown in Table 4, two highly-cytotoxic compounds (11 and 12) were also tested. Their structure and biological activity were described in a previous article [10]. The chemical structures of the test compounds suggests that they may intercalate with double-stranded nucleic acids.…”

The relationship between Hirshfeld potential and cytotoxic activity: a study along a series of flavonoid and chromanone derivatives

“…A comparison of the logP value (theoretical) with the contribution of various contacts to the Hirshfeld surface found that theoretical lipophilicity (logP) is also inversely proportional to the percentage contribution of the CÁ Á ÁC contacts to the Hirshfeld surface. This analysis has been extended by similar flavonoid compounds and benzylidenochromanone derivatives available from our previous research (Kupcewicz et al, 2013;Adamus-Grabicka et al, 2018;Suchojad et al, The cytotoxic activity (expressed as log 1 IC 50 ) against the HL-60, NALM-6, WM-115 and COLO-205 cancer cell lines.…”