Antibacterial Activities of 3-Substituted Coumarin-Scaffolds Synthesized under Microwave Irradiation

Hanhan Dianhar, Qonitatur Rifdah Tristiyana, Alfa Wezy Anugrah Purba, Sri Handayani, Purwantiningsih Sugita, Dyah Utami Cahyaning Rahayu


Global infections, such as diarrhea and acute respiratory disease, have urged the researchers in this area to discover coumarin-scaffold antibacterial agents, most widely used therapeutic drugs worldwide. This research aims to synthesize 3-substituted coumarins using microwave-assisted and evaluate their antibacterial activities against Escherichia coli and Staphylococcus aureus. In this study, salicylaldehyde with numerous activated methylenes has been used to synthesize 3-substituted coumarins following Knoevenagel condensation assisted by microwave irradiation. The highest yield of 3-acetylcoumarin was achieved using ethyl acetoacetate at the molar ratio of 1.2:1 (mol/mol) and 30 mol% of diethylamine using 100W microwave irradiation for 60 s under neat condition (43.65+0.50%). Moreover, ethyl coumarin-3-carboxylate (16.33%) was successfully synthesized using the optimum condition of 3-acetylcoumarin from diethyl malonate as activated methylene with a longer reaction time (900 s). However, the trial to afford 3-cyanocoumarin was failed from ethyl cyanoacetate and malononitrile as activated methylenes under the optimum condition of 3-acetylcoumarin. The inhibition zones of 3-acetylcoumarin and ethyl coumarin-3-carboxylate on disc diffusion assay towards E. coli at concentrations higher than 250 ppm showed weak activity, ranging from 1.9-3.6 mm. In contrast, both compounds showed no inhibition zone against S. aureus at all tested concentrations. This finding reveals that 3-substituted coumarins can be synthesized by low wattage microwave irradiation and solvent-free with moderate yield with ethyl acetoacetate is the most reactive methylene. Furthermore, this work proposes some corrections to assign proton and carbon chemical shifts in 3-substituted coumarins by analyzing HSQC and HMBC experiments in NMR measurement.


Keywords: antibacterial, coumarin, Knoevenagel condensation, microwave irradiation.


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