دورية أكاديمية
Stereochemistries and Biological Properties of Oligomycin A Diels-Alder Adducts.
| العنوان: | Stereochemistries and Biological Properties of Oligomycin A Diels-Alder Adducts. |
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| المؤلفون: | Omelchuk OA; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation., Malyshev VI; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russian Federation., Medvedev MG; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russian Federation.; National Research University Higher School of Economics, Myasnitskaya Street 20, Moscow 101000, Russian Federation., Lysenkova LN; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation., Belov NM; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation., Dezhenkova LG; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation., Grammatikova NE; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation., Scherbakov AM; Department of Experimental Tumor Biology, N. N. Blokhin National Medical Research Center of Oncology, Moscow 115522, Russian Federation., Shchekotikhin AE; Gause Institute of New Antibiotics, Moscow 119021, Russian Federation.; D. I. Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russian Federation. |
| المصدر: | The Journal of organic chemistry [J Org Chem] 2021 Jun 18; Vol. 86 (12), pp. 7975-7986. Date of Electronic Publication: 2021 May 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 2985193R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6904 (Electronic) Linking ISSN: 00223263 NLM ISO Abbreviation: J Org Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Columbus Oh : American Chemical Society Original Publication: Easton, Pa. [etc.] |
| مواضيع طبية MeSH: | Models, Molecular*, Humans ; MCF-7 Cells ; Molecular Conformation ; Oligomycins/pharmacology |
| مستخلص: | Oligomycin A is a potent antibiotic and antitumor agent. However, its applications are restricted by its high toxicity and low bioavailability. In this study, we obtained Oligomycin A Diels-Alder adducts with benzoquinone and N -benzylmaleimide and determined their absolute configurations by combining 1 H and ROESY NMR data with molecular mechanics conformational analysis and quantum chemical reaction modeling. The latter showed that adduct stereochemistry is controlled by hydrogen bonding of the Oligomycin A side-chain isopropanol moiety with the carbonyl group of the dienophile. Biological studies showed that the Diels-Alder modification of the Oligomycin A diene system resulted in a complex antiproliferative potential pattern. The synthesized adducts were determined to be more active against the triple-negative (ERα, PR, and HER2 negative) breast cancer cell line MDA-MB-231 and lung carcinoma cell line A-549 compared to Oligomycin A. Meanwhile, Oligomycin A was more potent against myeloid leukemia cell line K-562 and breast carcinoma cell line MCF-7 than its derivatives. Thus, modification of the diene moiety of Oligomycin A is a promising strategy for developing novel antitumor agents based on its scaffold. |
| المشرفين على المادة: | 0 (Oligomycins) 05HQS4AI99 (oligomycin A) |
| تواريخ الأحداث: | Date Created: 20210527 Date Completed: 20210707 Latest Revision: 20210707 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1021/acs.joc.1c00296 |
| PMID: | 34043357 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-6904 |
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| DOI: | 10.1021/acs.joc.1c00296 |