دورية أكاديمية
Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers
| العنوان: | Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers |
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| المؤلفون: | Yi Wang, Xiangli Zhang, Wenya Zhuang, Yanlei Yu, Xuanrong Sun, Hong Wang, Fengzhi Li, Qingyong Li |
| المصدر: | Molecules, Vol 27, Iss 12, p 3669 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Organic chemistry |
| مصطلحات موضوعية: | Camptothecin derivatives, cytotoxicity, bioavailability, Caco-2 cells model, drug resistance, Organic chemistry, QD241-441 |
| الوصف: | Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (Papp AP-BL) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10−6 cm/s and (2.48 ± 0.18) × 10−6 cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 27123669 1420-3049 |
| Relation: | https://www.mdpi.com/1420-3049/27/12/3669; https://doaj.org/toc/1420-3049 |
| DOI: | 10.3390/molecules27123669 |
| URL الوصول: | https://doaj.org/article/04a149ba86554f40be36b934c3fbbc2f |
| رقم الأكسشن: | edsdoj.04a149ba86554f40be36b934c3fbbc2f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 27123669 14203049 |
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| DOI: | 10.3390/molecules27123669 |