E)-(1-(4-Ethoxycarbonylphenyl)-5-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxystyryl)-2-pyrazoline: Synthesis, Characterization, DNA-Interaction, and Evaluation of Activity Against Drug-Resistant Cell Lines

• Published in: MolBank Vol. 2020; no. 1; p. M1114
• Main Authors: Matiadis, Dimitris, Mavroidi, Barbara, Panagiotopoulou, Angeliki, Methenitis, Constantinos, Pelecanou, Maria, Sagnou, Marina
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.03.2020
• Subjects: curcuminoids; cytotoxic; dna binding; mdr reversal; nitrogen heterocycles; pyrazolines
• ISSN: 1422-8599; 1422-8599
• DOI: 10.3390/M1114

(E)-1-(4-Ethoxycarbonylphenyl)-5-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxystyryl)-2-pyrazoline was synthesized via the cyclization reaction between the monocarbonyl curcuminoid (2E,6E)-2,6-bis(3,4-dimethoxybenzylidene)acetone and ethyl hydrazinobenzoate in high yield and purity (>95% by High-performance liquid chromatography (HPLC)). The compound has been fully characterized by 1H, 13C NMR, FTIR, UV-Vis and HRMS and its activity was evaluated in terms of its potential interaction with DNA as well as its cytotoxicity against resistant and non-resistant tumor cells. Both DNA thermal denaturation and DNA viscosity measurements revealed that a significant intercalation binding takes place upon treatment of the DNA with the synthesized pyrazoline, causing an increase in melting temperature by 3.53 ± 0.11 °C and considerable DNA lengthening and viscosity increase. However, neither re-sensitisation of Doxorubicin (DO X)-resistant breast cancer and multidrug resistance (MDR) reversal nor synergistic activity with DOX by potentially increasing the DOX cell killing ability was observed.