Chemoreversal Agents from Taiwanofungus Genus and Their More Potent Methyl Derivatives Targeting Signal Transducer and Activator of Transcription 3 (STAT3) Phosphorylation
| Autor: | Chin Fu Chen, Chin-Chuan Hung, I-Ting Wu, Hsin Yi Hung, Sio Hong Lam, Ko-Hua Yu, Ping Chung Kuo, Tian Shung Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
biology
Chemistry Pharmaceutical Science Pharmacology Article Multiple drug resistance RS1-441 chemistry.chemical_compound Pharmacy and materia medica Paclitaxel multidrug resistance Drug Discovery Cancer cell Taiwanofungus zhankuic acid STAT protein biology.protein Molecular Medicine Phosphorylation Medicine signal transducer and activator of transcription 3 (STAT3) STAT3 IC50 |
| Zdroj: | Pharmaceuticals Pharmaceuticals, Vol 14, Iss 916, p 916 (2021) Volume 14 Issue 9 |
| ISSN: | 1424-8247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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