A series of novel thio- and seleno-barbituric acid derivatives were synthesized by varying the substituents at N1 and N3 (ethyl, methyl, allyl, and phenyl), and C5 tethered with dienyl and trienyl moieties attached to substituents such as phenyl, 2-furanyl, 2-thiophenyl, 1-naphthyl, and 3-pyridyl. The cytotoxic potential of these derivatives was evaluated by using MTT assay against melanoma cell lines expressing either wild-type (CHL-1) or mutant (UACC 903) BRAF gene. Among all, 2b and 8b were identified as the most potent compounds. Both 2b and 8b inhibited viability of various melanoma cells and induced cell death as evidenced by Live and Dead assay. Western blot analysis showed that they induce PARP cleavage and inhibit anti-apoptotic Bcl-2, Bcl-xL and Survivin in a dose-dependent manner within 24 h of the treatment. Novel thiobarbituric acid analogs also inhibited viability of various other solid tumor cell lines, such as pancreatic, breast, and colon. Overall, 2b, 2d, and 8b emerged as the most effective compounds and make good leads for the development of future therapeutic agents.

通过改变N1和N3处的取代基（乙基，甲基，烯丙基和苯基）和C5与连接到取代基（如苯基，2-呋喃基，2-噻吩基，1-萘基和3-吡啶基。通过使用MTT分析针对表达野生型（CHL-1）或突变型（UACC 903）BRAF基因的黑素瘤细胞系，评估了这些衍生物的细胞毒性潜力。在所有化合物中，2b和8b被认为是最有效的化合物。无论2B和8B如活和死试验所证实的，其抑制了各种黑色素瘤细胞的活力并诱导了细胞死亡。Western印迹分析表明，它们在治疗的24小时内以剂量依赖的方式诱导PARP裂解并抑制抗凋亡的Bcl-2，Bcl-xL和Survivin。新型硫代巴比妥酸类似物还抑制了其他各种实体瘤细胞系（例如胰腺，乳腺和结肠）的生存能力。总体而言，2b，2d和8b成为最有效的化合物，为未来治疗剂的开发提供了良好的线索。