A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using ¹H NMR, ¹³C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds 1–21 were screened in vitro against Gram-positive bacterial strains such as Staphylococcus aureus and Bacillus subtilis and Gram-negative strains such as Escherichia coli and Pseudomonas aeruginosa. As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria. Compounds 2–6, oxadiazole derivatives, were found to have antibacterial activity that was 88 to 120% that of ciprofloxacin against Gram-positive and Gram-negative bacteria. The findings showed that none of the compounds tested had antifungal activity against Aspergillus flavus, but did have poor activity against Candida albicans, ranging from 23% to 33% of fluconazole, with compound 3 being the most active (33% of fluconazole). The most potent compounds, 3, 4, 5, and 6, displayed an IC₅₀ of 86, 42, 92, and 180 nM against E. coli DNA gyrase, respectively (novobiocin, IC₅₀ = 170 nM). Compounds 4, 5, and 6 showed IC₅₀ values (1.47, 6.80, and 8.92 µM, respectively) against E. coli topo IV in comparison to novobiocin (IC₅₀ = 11 µM).

A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In‐vitro screening of these hybrids against a full 60‐cell‐line panel at a single dose of 10 μM showed significant growth inhibition of up to 95 %. The most active compound showed in‐vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR. Apoptotic gene expression revealed that lead compounds induced MCF‐7 cell line apoptosis together with considerable change in the Bax/Bcl‐2 expression ratio. One lead compound led to a significant cell‐cycle S‐phase arrest, while another blocked the cell cycle at G1/S‐phase causing the accumulation of cells. Docking analysis of these two hybrids adopted the orientation and binding interactions with a higher liability to enter the active side pocket of HER2, L858R, and T790 M, preferable to that of co‐crystallized ligands. Modelling simulation was consistent with the acquired biological evaluation.