Background The alarming rise of multidrug-resistant microbial infections underscores the urgent need for novel antimicrobial agents.Aim A series of new pyrazole-based derivatives incorporating naphthalene and hydrazone pharmacophores were designed, synthesized, and studied for their antimicrobial activity with computational investigations.Materials and methods Two pyrazole-naphthalene-hydrazone hybrid types were synthesized and structurally characterized. The antimicrobial activity was systematically evaluated against Escherichia coli, Helicobacter pylori, Bacillus cereus, Staphylococcus aureus, and Candida albicans using the well diffusion method while investigating minimum inhibitory concentration (MIC). Molecular docking was also conducted to investigate the binding affinity of potent products against microbial targets (PDB IDs 3t88, 3ty7, and 5k04). Density function theory (DTF) investigation was also performed.Results and conclusion Compounds 3g and 4d demonstrated broad-spectrum antimicrobial activity with MIC values superior or comparable to the reference drug gentamicin. The results confirm that structural modifications at key positions on the pyrazole system, particularly with electron-withdrawing and bulky aromatic substituents, significantly enhanced activity. Molecular docking revealed enhanced binding interactions for possible inhibitory effects. DFT calculations showed insights into the electronic structure, molecular orbitals, and electrostatic potential of compound 3g. The results revealed the pyrazole–naphthalene hybrids as promising candidates for the development of new antimicrobial agents.
Alanzy et al. (Mon,) studied this question.