Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)-8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC₅₀ = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)-8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)-8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)-8i might be a potential drug candidate for OS treatment.

由于发病机制不明、药物靶点不明，目前尚无治疗骨肉瘤（OS）的药物上市。在此，噻唑烷酮1a通过具有结构多样性的内部世袭收集的表型筛选被发现为热门化合物。以下 SAR（结构-活性关系）研究提供了最终的水溶性先导化合物 ( R ) -8i，通过调节具有显着细胞效力的化合物的溶解度 (IC ₅₀  = 21.9 ) 作为 OS 细胞增殖的潜在抑制剂MNNG/HOS 细胞的 nM）和体内功效（小鼠体内 OS 生长抑制 52.9%）以及药代动力学特性。( R )- 8i还显着抑制体外OS 细胞迁移并显示出良好的耐受性。我们的初步调查表明 ( R ) -8i的作用不依赖于 p53 和肌铁蛋白 (MYOF)。这些结果表明 ( R )- 8i可能是 OS 治疗的潜在候选药物。