Design, Synthesis and Characterization of Novel (E)‐3‐(3‐Morpholino‐1‐(m‐Tolyl)‐5‐(Trifluoromethyl)‐1H‐Pyrazol‐4‐Yl)‐N‐Phenylacrylamide Derivatives and Their Antimicrobial, Antimalarial and Antitubercular Activities

This research investigates the design, synthesis, characterization, and biological assessment of a novel series of ( E )‐3‐(3‐morpholino‐1‐( m ‐tolyl)‐5‐(trifluoromethyl)‐1 H ‐pyrazol‐4‐yl)‐ N ‐phenylacrylamide derivatives (11a‐o) . The compounds (11a‐o) were synthesized via a multi‐step reaction sequence with 87%–96% yield in the final step and structurally confirmed using advanced spectroscopic techniques, including 1 H‐NMR, 13 C‐NMR, FT‐IR, and ESI‐MS. Analytical data confirm that the compound exhibits a purity of ≥ 95%. The biological evaluation encompassed antimicrobial, antimalarial, and antitubercular activity screening. Antimicrobial assays demonstrated notable antibacterial efficacy, with compounds 11h and 11j exhibiting superior potency compared to standard antibiotics against Escherichia coli and Staphylococcus aureus . Moderate antifungal activity was observed, with compound 11d displaying the highest inhibitory effect against Aspergillus niger . In antimalarial studies, compound 11i demonstrated exceptional activity (IC50 = 0.25 μg/mL) against Plasmodium falciparum , showing potency comparable to chloroquine. Additionally, compounds 11a and 11i exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv. A structure–activity relationship (SAR) analysis revealed that specific chemical modifications, particularly electron‐withdrawing substitutions and morpholino moieties, played a crucial role in enhancing antimalarial activity. These findings highlight the potential of these derivatives as promising lead compounds for further development into effective therapeutics targeting drug‐resistant bacterial, fungal, malarial, and tubercular infections.