Ultrasonic Wave-Assisted Synthesis of Chalcone Based Pyrazoline Compound and Evaluation of Its Antimicrobial and Cytotoxic Activities

Abstract

Chalcone-based pyrazoline compounds are known for their potential antibacterial properties. Previous studies have reported their synthesis via one- or two-step reflux procedures. This study aimed to synthesize and evaluates the antimicrobial and cytotoxic activities of chalcone-based pyrazoline compound. A pyrazoline compound, 4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl)-N,N-dimethylaniline (PPA), was synthesized through the formation of 4-dimethylamino chalcone (DAC) using a Claisen–Schmidt condensation, followed by cyclization of its α,β-unsaturated carbon system into a pyrazoline ring. Ultrasonic irradiation was used to assist the reaction, employing both one-pot and two-pot synthesis methods. The resulting compounds were evaluated for yield, structural characteristics, antimicrobial activity, and cytotoxicity. Antibacterial activity was assessed through in silico molecular docking and in vitro minimum inhibitory concentration (MIC) tests. Cytotoxicity was evaluated using the Brine Shrimp Lethality Test (BSLT). Both synthesis methods successfully produced PPA, but TLC analysis revealed that the two-pot method yielded a purer product with a higher yield (99%). The antimicrobial activity evaluation showed that both DAC and PPA exhibited weak antimicrobial activity, with MIC values of 5000 µg/mL against Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Candida albicans. In the cytotoxicity assay, PPA exhibited significantly lower toxicity (LC₅₀ = 81.27 µg/mL) than DAC (LC₅₀ = 0.0042 µg/mL). These findings suggest that conversion of the α,β-unsaturated system to a pyrazoline ring structure reduces the compound’s cytotoxicity.