In Vitro Anticancer Activity and In Silico Target Profiling of 5-(Piperazin-1-ylsulfonyl)-1,3-oxazole-4-carbonitriles

Sulfonylated 5-piperazine-substituted 1,3-oxazole-4-carbonitriles were synthesized and evaluated for in vitro anticancer activity. Cytotoxicity was assessed in hepatocellular (HepG2, Huh7), breast (MCF-7, MDA-MB-231), cervical (HeLa), melanoma (M21), and neuroblastoma (Kelly, SH-SY5Y) cell lines, with HEK293 cells used as a non-malignant control. Compounds 7a, 7b, and 8aa emerged as lead structures. Notably, compound 7b showed the highest activity in Kelly neuroblastoma cells (IC₅₀ = 1.3 µM) while exhibiting low cytotoxicity toward HEK293 cells (IC₅₀ > 10 µM), indicating an improved selectivity profile relative to doxorubicin. In silico molecular docking suggested favorable interactions of the lead compounds with several cancer-associated proteins, with the highest predicted affinity observed for Aurora A kinase, along with additional predicted interactions with cyclin-dependent kinases. Predicted ADMET properties of compounds 7a, 7b, and 8aa compared favorably with doxorubicin, although the lead compounds were not readily biodegradable under OECD 301D conditions. Overall, these findings identify oxazole-4-carbonitriles as promising anticancer candidates with a putative kinase-directed mechanism of action.