Novel N-phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy
文献类型：期刊论文
| 作者 | Peng, Yan; Peng, Ying; Zhang, Wei; Zhang, Siyi; Peng, Huiqian; Li, Zhen; Li, Bo; Liu, Linyi; Zhuo, Linsheng; Wang, Zhen |
| 刊名 | FRONTIERS IN PHARMACOLOGY
 |
| 出版日期 | 2024 |
| 卷号 | 15 |
| 英文摘要 | Introduction N-phenyl-2-(aniline) analog N53 is a previously discovered dual inhibitor of Topo I and COX-2, which exhibited significant anti-colon cancer activity in vitro, but the poor solubility and moderate anti-cancer activity in vivo hindered its further development.Methods To rectify the suboptimal drug properties of N53, a series of salt forms were developed and further evaluated through in vivo and in vitro experiments.Results The hydrochloride (N53HCl) has a well-characterized crystal structure and its solubility reached 540.1 mu g/mL, which is nearly 1,700 times higher than that of N53 (0.32 mu g/mL). Increasing the N53 solubility consistently promotes its effective concentration, further enhancing the COX-2/Topo I inhibitory activity and the anti-tumor activity in vitro (IC50 values of 2.95 +/- 0.08 mu M for HT29 cells, 7.99 +/- 0.85 mu M for RKO cells, 10.94 +/- 1.30 mu M for HCT116 cells), as well as the anti-proliferative and pro-apoptotic activity. Meanwhile, its oral pharmacokinetic property in vivo is also improved. The elimination half-life (T1/2) is prolonged from 10.78 to 22.29 h, the maximum plasma concentration (Cmax) is increased 2-fold, and the area under the plasma drug concentration-time curve (AUC0-infinity) is increased 3-fold. In colon cancer xenograft mouse models, the tumor inhibition rate of N53HCl was 53.7%, superior to that of N53 (34.7%). Moreover, the results of HE staining showed that N53HCl had no obvious toxic effects and side effects on other organs, indicating that it was safe in vivo.Discussion This study demonstrated that N53HCl exhibits superior pharmacokinetic properties, anti-colon cancer efficacy, and safety, providing a promising drug candidate for colon cancer therapy. |
| 源URL | [http://210.75.249.4/handle/363003/61918]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 推荐引用方式 GB/T 7714 | Peng, Yan,Peng, Ying,Zhang, Wei,et al. Novel N-phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy[J]. FRONTIERS IN PHARMACOLOGY,2024,15. |
| APA | Peng, Yan.,Peng, Ying.,Zhang, Wei.,Zhang, Siyi.,Peng, Huiqian.,...&Jiang, Weifan.(2024).Novel N-phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy.FRONTIERS IN PHARMACOLOGY,15. |
| MLA | Peng, Yan,et al."Novel N-phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy".FRONTIERS IN PHARMACOLOGY 15(2024). |
入库方式： OAI收割
来源：西北高原生物研究所
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