: In continuation of our efforts to find new antimicrobials, herein we report the synthesis of various pyrazole, pyrazoline, and pyridine based novel bioactive heterocycles (3a-t). Newly synthesized compounds analysed for their antimicrobial activity. Compounds 3c, 3h, 3i, 3k, 3n, and 3q were showed significant antimicrobial activity. Molecular docking study for the most active analogues DNA gyrase subunit b (PDB ID: 1KZN) corroborated well with observed antimicrobial potency exhibiting significant binding affinity. For the interpretation of the chemical structures reported in this paper were based on IR, 1H NMR, 13C NMR, and mass spectral data.