Chemoreversal agents from Taiwanofungus genus and their more potent methyl derivatives targeting signal transducer and activator of transcription 3 (STAT3) phosphorylation

Ko Hua Yu, Chin Chuan Hung, Tian Shung Wu, Chin Fu Chen, I. Ting Wu, Ping Chung Kuo, Sio Hong Lam, Hsin Yi Hung

研究成果: Article同行評審

摘要

Multidrug resistance (MDR), for which the mechanisms are not yet fully clear, is one of the major obstacles to cancer treatment. In recent years, signal transducer and activator of transcription 3 (STAT3) were found to be one of the important MDR mechanism pathways. Based on the previous research, zhankuic acid A, B, and C were found to have collateral sensitivity effects on MDR cancer cells, and MDR inhibitory activity of zhankuic acid methyl ester was found to be better than that of its acid. Therefore, we executed a systematic examination of the structure–activity relationship of zhankuic acid methyl ester derivatives to collateral sensitivity in MDR cancer cells. The results showed that compound 12 is the best in terms of chemoreversal activity, where the reversal fold was 692, and the IC50 value of paclitaxel combined with 10 μM compound 12 treatment was 1.69 nM in MDR KBvin cells. Among all the derivatives, methyl ester compounds were found to be better than their acids, and a detailed discussion of the structure–activity relationships of all of the derivatives is provided in this work. In addition, compounds 8, 12, and 26 were shown to influence the activation of STAT3 in KBvin cells, accounting for part of their chemoreversal effects. Our results may provide a new combined therapy with paclitaxel to treat multidrug-resistant cancers and provide a new therapy option for patients.

原文English
文章編號916
期刊Pharmaceuticals
14
發行號9
DOIs
出版狀態Published - 2021 九月

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 藥學科學
  • 藥物發現

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