(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

Abstract

(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.

Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

“…Elemental analyses were performed using a PerkinElmer 2400 CHNS 100V Organic Elemental Analyzer (Waltham, MA, USA). Compounds 5-7 were synthesised as described previously [27][28][29].…”

“…As part of an effort to develop improved curcuminoids, the design of monocarbonyl analogs of curcumin (MACs) as a highly attractive alternative class of compounds was chosen [27][28][29]. MACs usually demonstrate higher potency than the diketo-curcuminoid counterparts, they are more readily produced, more stable, and they exhibit improved pharmacological profiles [39,40].…”

“…Thus, symmetric compounds 1-4 were prepared by a conventional Claisen-Schmidt reaction from the corresponding aromatic aldehydes and acetone or cyclohexanone, by using a catalytic amount of concentrated hydrochloric acid (Scheme 1). In a similar approach, symmetric compounds 8-10 were synthesized from the methoxyprotected intermediates 5-7, prepared from the corresponding aromatic aldehydes and acetone or cyclohexanone, in alkaline conditions (Scheme 2) [28]. It is worth noting that the Claisen-Schmidt condensation of the unprotected aldehyde coupling partners did not proceed well in these conditions.…”

Pyrazol(in)e Derivatives of Curcumin Analogs As a New Class of Anti- Trypanosoma Cruzi Agents

“…13 C: δ = 39.52 ± 0.06 ppm). Elemental analyses were performed… Starting materials 1a-c, 1e-g and 1i,j were prepared following our published procedures [32,34]. Pyrazolines 2a, 5a-c and pyrazoles 6a,b were prepared according to our published protocols without modifications [27,[32][33][34][35].…”

Curcumin Derivatives as Potential Mosquito Larvicidal Agents against Two Mosquito Vectors, Culex pipiens and Aedes albopictus

“…LC50 and LC 90 values of four compounds against the third-to fourth-instar larvae of Aedes albopictus and Culex pipiens biotype molestus after 24 h exposure (SE: standard error; d.f. : degrees of freedom).…”