Development of New Multicomponent Reactions in Eco-Friendly Media-Greener Reaction and Expeditious Synthesis of Novel Bioactive Benzylpyranocoumarins

Hamida Jelali,A Chakchouk-Mtibaa,Yaser Bathich,L Mellouli,Lasaad Baklouti,Hallouma Bilel,Naceur Hamdi

doi:10.1155/2019/8693614

Hamida Jelali, A Chakchouk-Mtibaa + Show 5 more

Open Access

https://doi.org/10.1155/2019/8693614

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Abstract

Multicomponent cyclocondensation of hydrazine derivatives, ethyl acetoacetate, aromatic aldehydes, and 4-hydroxycoumarin has been reported. The optimization details of the developed novel protocol are recorded. The novel procedure features short reaction time, moderate yields, and simple workup. In addition, BMIM[triflate] was chosen as a green solvent. The structures of the obtained benzylpyrazolyl coumarins were determined and confirmed by 1H NMR, 13C NMR, IR, and elemental analysis. The MIC values of benzylpyrazolyl coumarin derivatives were determined by the microbroth dilution method using 96-well plates. However, the derivatives 5a, 5b, 5d, and 5g possess the strongest activities. Compound 5b was the most active derivative against Candida albicans. Moreover, the antioxidant activity determination of these coumarins derivatives 5(a–g)–6(a–g) were studied with the DPPH and compared with gallic acid (GA)and butylated hydroxytoluene (BHT). Molecular modelling studies using DFT (density functional theory) calculations showed that there two tautomers A and B in which A is more stable than B. The benzylpyrazolyl coumarin derivatives 5e and 6f exhibited the most cytotoxic effect on the promising cytotoxic activity with IC50 values 4.45 μg/mL against MDA-MB-231 and 4.85 μg/mL against MCF7, respectively.

Highlights

Coumarin scaffolds are commonly bioactive compounds [1–23]
BMIM[triflate] was chosen as a green solvent. e structures of the obtained benzylpyrazolyl coumarins were determined and confirmed by 1H NMR, 13C NMR, IR, and elemental analysis. e minimum inhibitory concentrations (MICs) values of benzylpyrazolyl coumarin derivatives were determined by the microbroth dilution method using 96-well plates
Molecular modelling studies using DFT calculations showed that there two tautomers A and B in which A is more stable than B. e benzylpyrazolyl coumarin derivatives 5e and 6f exhibited the most cytotoxic effect on the promising cytotoxic activity with IC50 values 4.45 μg/mL against MDA-MB-231 and 4.85 μg/mL against MCF7, respectively

Summary

Introduction

Coumarin scaffolds are commonly bioactive compounds [1–23]. Pyrazolone derivatives exhibit a broad spectrum of biological activities [24–26] and are important structural moieties in many drug substances of medicinal applications [22, 27, 28], such as phenazone, propyphenazone, ampyrone, and metamizole sodium (Figure 1).Multicomponent reactions convert three or more starting materials in one pot to a highly functionalized product displaying maximum molecular diversity [29–35].At present, ionic liquids (ILs) are playing a more and more important role in organic synthesis as green catalysts and solvents. E structures of the obtained benzylpyrazolyl coumarins were determined and confirmed by 1H NMR, 13C NMR, IR, and elemental analysis.

Results

Conclusion