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 <b>7a</b>, <b>7b</b>, and <b>8aa</b> emerged as lead structures. Notably, compound <b>7b</b> 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 <b>7a</b>, <b>7b</b>, and <b>8aa</b> 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.