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Synthesis and biological evaluation of novel isoxazoloquinone derivatives as potent STAT3-targeting antipsoriasis agents.
Chen, Ling; Zhu, Shuaiwen; Xie, Yuanzhu; Wang, Liuliu; Gao, Jinlei; Luo, Tiao; Li, Jijia; Deng, Xu; Ma, Dayou; Liu, Suyou; Luo, Zhiyong.
Afiliação
  • Chen L; Department of Biochemistry and Molecular Biology, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China.
  • Zhu S; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China.
  • Xie Y; Department of Biochemistry and Molecular Biology, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China.
  • Wang L; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China.
  • Gao J; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China.
  • Luo T; Department of Biochemistry and Molecular Biology, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China.
  • Li J; Department of Biochemistry and Molecular Biology, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China.
  • Deng X; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China.
  • Ma D; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China. Electronic address: madayou@csu.edu.cn.
  • Liu S; Xiangya School of Pharmaceutical Sciences, Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha, China. Electronic address: suyouliu@csu.edu.cn.
  • Luo Z; Department of Biochemistry and Molecular Biology, School of Life Sciences, Xiangya School of Medicine, Central South University, Changsha, China. Electronic address: luozhiyong@csu.edu.cn.
Bioorg Chem ; 151: 107617, 2024 Jul 08.
Article em En | MEDLINE | ID: mdl-39053100
ABSTRACT
Psoriasis is a troublesome scaling skin disease with no high-effective medication available by far. Signal transducer and activator of transcription 3 (STAT3) has recently been revealed as a crucial player in the pathogenesis and progression of psoriasis and emerged as an intriguing antipsoriatic drug target. Naturally occurring lapachol and its quinone analogs had been discovered as effective STAT3 inhibitors, however, their antipsoriatic effects are not well investigated. Previously, we have reported a series of isothiazoloquinone lapachol derivatives. Here, the antipsoriastic potentials of these isothiazoloquinones were investigated and, in addition, 35 novel isoxazoloquinone derivatives were prepared and studied for their anti-psoriasis properties. Among them, the most potent antipsoriatic compound B20 determined by in vitro test on HaCaT cells could directly bind to STAT3, reduce STAT3 level and inhibit STAT3 nuclear translocation. In vivo studies showed that topical application of B20 could effectively alleviate IMQ-induced psoriasis in mice with no obvious side effects. In addition, B20 inhibited the production of interleukin 17 (IL-17A), a STAT3-downstream cytokine essential for the progression of psoriasis, both in vitro and in vivo. Thus, isoxazoloquinone B20 is a potent STAT3-targeting antipsoriatic agent worth of further investigation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Bioorg Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Bioorg Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China