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 Y, Pi R, Niu L, Zhao Y, Ni D, Song L, Li Z, Han W, Wei Q, Han Y, Zhu T, Luo Z, Sun D, Dong S, and Liu S
- Subjects
- Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Bone Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred ICR, Mice, Nude, Molecular Structure, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Osteosarcoma pathology, Pyridines chemical synthesis, Pyridines chemistry, Structure-Activity Relationship, Thiazolidines chemical synthesis, Thiazolidines chemistry, Antineoplastic Agents pharmacology, Bone Neoplasms drug therapy, Osteosarcoma drug therapy, Pyridines pharmacology, Thiazolidines pharmacology
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)- Published
- 2022
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