The development of novel antimicrobial and anticancer agents remains a priority due to rising drug resistance and high systemic toxicity of current treatments. A series of novel pyrazole (2–6), pyrimidine (7–10), and pyridine/oxazinone (11–14) derivatives were synthesized from a chalcone scaffold (1). They were evaluated for antimicrobial, antibiofilm (Pseudomonas aeruginosa), and cytotoxic (HepG2 cells) activities. Molecular docking and qRT-PCR were performed to study their mechanism. Pyrazoles 3–5 and oxazinone 13 showed potent antibacterial activity against S. aureus (MIC = 2–3.12 µg/mL). Compounds 4 and 13 effectively eradicated P. aeruginosa biofilms, achieving a ≥ 5 log10 reduction within 4 h at 0.8 × MIC, driven by disruption of the bacterial respiratory chain. For anticancer activity, compounds 10 and 13 selectively reduced HepG2 cell viability to 35–40% via oxidative stress-mediated apoptosis. Mechanistically, compound 4 reduced gyrB expression in E. coli by approximately 4.6-fold, while molecular docking supported its interaction with the ATP-binding pocket of DNA gyrase. Overall, the functionalized heterocycles, particularly compounds 4 and 13, represent promising dual-acting candidates with potent antibacterial, antibiofilm, and selective anticancer activities.
A. Hassan, E. S. Essam, Selwan Hamed et al.· Scientific Reports· 0 citations
The emergence of antimicrobial resistance needs the development of new chemotherapeutic scaffolds. Pyrazole derivatives are recognized for their broad biological activity; however, further structural innovation is required to enhance antimicrobial efficacy and safety. Thus, new pyrazole-based candidates were designed and synthesized using 3-(4-chlorophenyl)-1-phenylpyrazol-4-yl-2-cyanoacryloyl chloride as a versatile precursor. A series of mono- and bidentate nucleophile-derived compounds was prepared and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans. Several derivatives exhibited potent antibacterial and antifungal activity, particularly against Gram-positive strains, with minimum inhibitory concentrations comparable to standard drugs. Most compounds showed low cytotoxicity toward HepG2 cells, which was further reduced upon antioxidant co-treatment. Notably, vitamin C and N-acetylcysteine showed synergistic enhancement of antimicrobial and antibiofilm effects. Molecular docking studies against dihydropteroate synthase (DHPS, PDB: 5U0V) revealed favorable binding interactions, with the thiophene-based derivative 10 displaying ligand efficiency comparable to the co-crystallized ligand 7VJ. Overall, these findings highlight pyrazole-based scaffolds as promising antimicrobial candidates with favorable biological profiles, providing a strong basis for further structural optimization.
E. El‐Helw, Selwan Hamed, A. El-ziaty et al.· Scientific Reports· 0 citations
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