3-benzazecine-based cyclic allene derivatives as highly potent P-glycoprotein inhibitors overcoming doxorubicin multidrug resistance
| العنوان: | 3-benzazecine-based cyclic allene derivatives as highly potent P-glycoprotein inhibitors overcoming doxorubicin multidrug resistance |
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| المؤلفون: | Maxim S. Kobzev, Alexander A. Titov, Saverio Cellamare, Modesto de Candia, Alexey V. Varlamov, Mauro Niso, Tatiana N. Borisova, Leonid G. Voskressensky, Nicola Antonio Colabufo, Leonardo Pisani, Cosimo Altomare |
| المصدر: | Future Medicinal Chemistry. 11:2095-2106 |
| بيانات النشر: | Future Science Ltd, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Allene, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Neoplasms, Drug Discovery, medicine, Humans, Doxorubicin, ATP Binding Cassette Transporter, Subfamily B, Member 1, Cytotoxicity, Cell Proliferation, 030304 developmental biology, P-glycoprotein, Pharmacology, Aza Compounds, 0303 health sciences, P-glycoprotein Inhibitor, Antibiotics, Antineoplastic, biology, Chemistry, Molecular biology, Drug Resistance, Multiple, In vitro, Alkadienes, Multiple drug resistance, Cyclization, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Multidrug Resistance-Associated Protein 1, medicine.drug |
| الوصف: | Aim: Enamino 3-benzazecine compounds, incorporating the C6-C8 allene system, were synthesized and evaluated in vitro as inhibitors of P-glycoprotein (P-gp) and/or multidrug resistance-associated protein 1 (MRP1), two efflux pumps mainly connected with multidrug resistance (MDR) in cancer cells. Results & methodology: Most of the synthesized compounds were selective P-gp inhibitors in Calcein-AM uptake assay. Structure–activity relationships (SARs) pointed out that CO2Me derivatives are more potent than acetyl derivatives, and 10,11-dimethoxy compounds are five to tenfold more potent inhibitors than the respective unsubstituted compounds, and that the P-gp inhibition potency is mainly related to volume parameters. Conclusion: Nanomolar P-gp inhibitors, such as 23 (IC50 = 4.2 nM), restored the antiproliferative activity of doxorubicin in multidrug-resistant cells. The observed activities showed that 3-benzazecine-based compounds may be promising MDR reversers. |
| تدمد: | 1756-8927 1756-8919 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fb6da2de720f4de3840b4d151cc7946 https://doi.org/10.4155/fmc-2019-0037 |
| رقم الأكسشن: | edsair.doi.dedup.....8fb6da2de720f4de3840b4d151cc7946 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 17568927 17568919 |
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