2. Academic Validation
  3. Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo

Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo

  • Eur J Med Chem. 2022 Jan 15;228:114010. doi: 10.1016/j.ejmech.2021.114010.
Yaqi Deng 1,  Rou Pi 1,  Li Niu 1,  Yun Zhao 1,  Dan Ni 1,  Longlong Song 1,  Zi Li 1,  Wangyujing Han 1,  Qinghua Wei 1,  Yuqiao Han 1,  Tong Zhu 1,  Zhengli Luo 1,  Donghui Sun 1,  Suzhen Dong 2,  Shunying Liu 3
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China.
  • 2 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China. Electronic address: szdong@brain.ecnu.edu.cn.
  • 3 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China. Electronic address: syliu@sist.ecnu.edu.cn.
PMID: 34861640 DOI: 10.1016/j.ejmech.2021.114010
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 (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.

Keywords

Inhibitors; Osteosarcoma; Phenotypic screening; Thiazolidinone.

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