1. Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo.
- Author
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Deng, Yaqi, Pi, Rou, Niu, Li, Zhao, Yun, Ni, Dan, Song, Longlong, Li, Zi, Han, Wangyujing, Wei, Qinghua, Han, Yuqiao, Zhu, Tong, Luo, Zhengli, Sun, Donghui, Dong, Suzhen, and Liu, Shunying
- Subjects
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CELL proliferation , *CELL migration , *STRUCTURE-activity relationships , *DRUG target , *OSTEOSARCOMA - Abstract
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 (IC 50 = 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. [Display omitted] • Thiazolidinones were discovered for treating osteosarcoma by phenotypic screening. • The screening used an in-house patrimonial collection of structural diversity. • Lead compound (R)- 8i selectively inhibit osteosarcoma cell in vitro and in vivo. • (R)- 8i also significantly suppresses osteosarcoma cell migration in vitro. • (R)- 8i presents a considerable bioavailability and a low toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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