دورية أكاديمية
Syntheses and structure-activity relationships of taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III.
| العنوان: | Syntheses and structure-activity relationships of taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III. |
|---|---|
| المؤلفون: | Ojima I; Department of Chemistry, State University of New York at Stony Brook 11794-3400, USA., Slater JC, Kuduk SD, Takeuchi CS, Gimi RH, Sun CM, Park YH, Pera P, Veith JM, Bernacki RJ |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 1997 Jan 31; Vol. 40 (3), pp. 267-78. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Taxoids*, Antineoplastic Agents, Phytogenic/*chemical synthesis , Antineoplastic Agents, Phytogenic/*pharmacology , Paclitaxel/*analogs & derivatives, ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/metabolism ; Docetaxel ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Conformation ; Molecular Structure ; Paclitaxel/chemical synthesis ; Paclitaxel/chemistry ; Paclitaxel/metabolism ; Paclitaxel/pharmacology ; Structure-Activity Relationship ; Tumor Cells, Cultured |
| مستخلص: | A series of new taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III was synthesized by means of the beta-lactam synthon method. Most of the new taxoids thus synthesized possess excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines, and several of these taxoids show subnanomolar IC50 values which are severalfold to 1 order of magnitude better than those of paclitaxel and docetaxel. Modifications at the 3'- and 3'-N-positions exert marked effects on the activity. For the substituents at C-3', the cytotoxicity decreases in the order 2-furyl approximately 2-methyl-1-propenyl > or = 2-methylpropyl > (E)-1-propenyl > or = n-propyl > phenyl > > 2,2-dimethylpropyl. For the 3'-N substituents, the activity decreases in the order t-BuOCO > Ph > n-hexanoyl. A significant increase in the cytotoxicity against the doxorubicin-resistant human breast cancer cell line MCF7-R that expresses the multidrug resistance (MDR) phenotype is observed by the proper modification of the substituent at C-10. The observed remarkable effects of the substituents at C-10 on the activity against MCF7-R can be ascribed to the effective inhibition of the binding of these new taxoids to P-glycoprotein that is responsible for MDR. |
| معلومات مُعتمدة: | GM427980 United States GM NIGMS NIH HHS; NCI 13038 United States CI NCPDCID CDC HHS |
| المشرفين على المادة: | 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) 0 (Antineoplastic Agents, Phytogenic) 0 (Taxoids) 15H5577CQD (Docetaxel) P88XT4IS4D (Paclitaxel) |
| تواريخ الأحداث: | Date Created: 19970131 Date Completed: 19970313 Latest Revision: 20181130 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1021/jm960563e |
| PMID: | 9022793 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 0022-2623 |
|---|---|
| DOI: | 10.1021/jm960563e |