دورية أكاديمية
Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors.
| العنوان: | Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors. |
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| المؤلفون: | Khusnutdinova EF; Ufa Institute of Chemistry UFRS RAS, 71 pr. Oktyabrya, Ufa 450054, Russian Federation. Electronic address: elmaH@inbox.ru., Petrova AV; Ufa Institute of Chemistry UFRS RAS, 71 pr. Oktyabrya, Ufa 450054, Russian Federation; Bashkir State University, 32 Validy Str., Ufa 450076, Russian Federation., Thu HNT; Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay Dist., Hanoi, Viet Nam., Tu ALT; Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay Dist., Hanoi, Viet Nam., Thanh TN; Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay Dist., Hanoi, Viet Nam., Thi CB; Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str., Cau Giay Dist., Hanoi, Viet Nam., Babkov DA; Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation., Kazakova OB; Ufa Institute of Chemistry UFRS RAS, 71 pr. Oktyabrya, Ufa 450054, Russian Federation. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2019 Jul; Vol. 88, pp. 102957. Date of Electronic Publication: 2019 Apr 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| مواضيع طبية MeSH: | Drug Design*, Glycoside Hydrolase Inhibitors/*pharmacology , Indoles/*pharmacology , alpha-Glucosidases/*metabolism, Dose-Response Relationship, Drug ; Glycoside Hydrolase Inhibitors/chemical synthesis ; Glycoside Hydrolase Inhibitors/chemistry ; Humans ; Indoles/chemical synthesis ; Indoles/chemistry ; Models, Molecular ; Molecular Structure ; Structure-Activity Relationship |
| مستخلص: | A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction. To compare the influence of the fused indole or the seven-membered A-ring on the inhibitory activity, lupane A-azepanones with different substituents at C28 were synthesized. The structure-activity relationships revealed that the enzyme inhibition activity dramatically increased (up to 4730 times) when the carboxylic group of 2,3-indolo-betulinic acid was converted to the corresponding amide. Thus, the IC (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acarbose; Betulinic acid; Indole; Lupanes; Natural products; Synthesis; Triterpenoids; Type II diabetes; α-Glucosidase inhibitor |
| المشرفين على المادة: | 0 (Glycoside Hydrolase Inhibitors) 0 (Indoles) EC 3.2.1.20 (alpha-Glucosidases) |
| تواريخ الأحداث: | Date Created: 20190512 Date Completed: 20200922 Latest Revision: 20200922 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.bioorg.2019.102957 |
| PMID: | 31077913 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2019.102957 |