Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos

This study aimed to compare and evaluate the growth inhibition effects of eight previously synthesized compounds, cis-3,4-diaryl-α-methylene-γ-butyrolactams (compounds 1–8), on two human renal carcinoma cell (RCC) lines: CRL-1932 (rapid growth) and HTB-44 (slow growth). MTT assays and flow cytometry were conducted, revealing that compounds 5 and 6 had the potential to induce cell death in the slow-growing RCC cells (HTB-44), while compound 8 demonstrated effectiveness in both RCC lines (HTB-44 and CRL-1932). Additionally, a non-transformed HEK293 cell line and a transgenic zebrafish with a green fluorescent kidney Tg(wt1b:egfp) were used to assess the toxicities of compounds 5, 6, and 8. The findings suggested that compound 8 was relatively non-toxic compared to the others. Western blot analysis indicated that compounds 5, 6, and 8 may interact with the P53/mTOR pathways. Based on these results, we concluded that compound 8 exhibits RCC growth inhibition properties and has lower toxicity, making it a candidate for further investigation in mammalian models.