A lead compound with the (1,3,4-thiadiazol-2-yl)-acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC₅₀ values of 1-5 μM on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC₅₀ > 50 μM on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.

在基于内部细胞的筛选中，发现具有（1,3,4-噻二唑-2-基）-丙烯酰胺支架的先导化合物对几种肿瘤细胞系具有明显的细胞毒性。然后合成了总共60种衍生物，并在CCK-8细胞活力测定中进行了测试。其中一些表现出改善的细胞毒活性。最有效的化合物在两种急性白血病肿瘤细胞系（即RS4; 11和HL-60）上的IC ₅₀值为1-5μM。几种活性化合物的流式细胞仪分析和caspase活化检测表明它们诱导了caspase依赖性凋亡。令人鼓舞的是，这些化合物对正常细胞没有明显的细胞毒性，即IC ₅₀在HEK-293T细胞上> 50μM。尽管尚未揭示此类化合物的分子靶标，但我们目前的结果表明，此类化合物代表了开发针对急性白血病的候选药物的新可能性。