Synthesis and Characterization of Some New Coumarin Derivatives as Probable Breast Anticancer MCF-7 Drugs

Ahmed Gaber,Ibrahim M El-Deen,Abdulhakeem S Alamri,Walaa F Alsanie,Moamen S Refat,Majid Alhomrani

doi:10.3390/cryst11050565

Ahmed Gaber, Ibrahim M El-Deen + Show 4 more

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https://doi.org/10.3390/cryst11050565

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Journal: Crystals	Publication Date: May 19, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Taif University, Port Said University

Abstract

This study aimed to synthesize quinolinone derivatives and investigate their cytotoxic activity. The compound 1-azacoumarin-3-carboxylic acid (2-oxo-1H-quinoline-3-carboxylic acid) was obtained via the cyclocondensation of 2-hydroxybenzaldehyde with diethyl malonate in base catalyst to give ethyl coumarin-3-carboxylate, followed by the ammonolysis of ester (ethyl coumarin-3-carboxylate) with ammonia in the presence of anhydrous potassium carbonate. Treatment of 2-oxo-1H-quinoline-3-carboxylic acid with acetic anhydride, cinnamaldehyde, cinnamic acid and methyl 5-phenyl-2-cyano-2,4-pentadienoate under different conditions led to the formation of 1 (substituted) aza coumarin-3-carboxylic acids (1-N-(acetyl)-azacoumarin-3-carboxylic acid, 1-N-(2-Formyl-1-phenyl) vinyl-azacoumarin-3-carboxylic acids, 1-N-[2-(Hydroxy) carbonyl-1-(Phenyl) vinyl]-azacoumarin-3-carboxylic acid and 1-N-(4-Cyano-5-methoxy-5-oxo-1-Phenylpenta-1,3-diene-1-y)-azacoumarin-3-carboxylic 284 acid), respectively. The structures of synthesized 1-(substituted) azacoumarin-3-carboxylic acids were confirmed based on spectroscopic methods (IR and NMR), along with elemental analyses. Interestingly compound 6 demonstrated probable impacts as an anti-cancer drug against the MCF-7 cell line. The mechanism of action was assessed using a flow cytometric assay. The outcomes revealed that compound 6 could arrest the cell cycle at G2/M phase and pre-G1 apoptosis.

Highlights

Coumarins can be synthesized using a variety of methods, including the Perkin reaction, Knoevenagel condensation, Pechmann condensation, Wittig reaction, Baylis–Hillman reaction, Claisen rearrangement, and Vilsmeier–Haack and Suzuki cross-coupling reactions [1]
Tionally, the design of sulfamide 3-benzylcoumarin hybrids bearing an oxadiazole ring at the design of sulfamide 3-benzylcoumarin hybrids bearing an oxadiazole position 7 has enabled the preparation of new multitarget mitogen-activated protein kinase inhibitors and nitric oxide donors, both of which can be used due to their antiproliferative properties [36]. Encouraged by these observations and in continuation the work on the studies of coumarin as an anti-cancer drug, we report the synthesis of a new class of azacoumarin-3carboxylic acid derivatives to determine the appropriate replacement/addition of different
(3) (0.01 mole), andbyα,β-5-unsaturated carbonyl compounds (namely, coumarin as an anti-cancer drug, we report the synthesis of a new class of azacoumarincinnamic, acid and methyl 5-phenyl-2-cyano-2,4-pentadine oats (0.01 mole))

Summary

Introduction

Coumarins can be synthesized using a variety of methods, including the Perkin reaction, Knoevenagel condensation, Pechmann condensation, Wittig reaction, Baylis–Hillman reaction, Claisen rearrangement, and Vilsmeier–Haack and Suzuki cross-coupling reactions [1]. Many studies on the medicinal properties of coumarins have been published [2]. Several coumarin derivatives have been shown to have antioxidant activity [5]. Some coumarins have been synthesized as acetylcholinesterase (AchE) inhibitors, which may be used to treat Alzheimer’s disease [6]. Coumarins have a variety of biological properties, including anti-inflammatory [7], anti-HIV [8], anticancer [9], antituberculosis [10], anticoagulant [11], antiviral [12], and antihyperglycemic characteristics [13]

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