تقرير
Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates.
| العنوان: | Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates. |
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| المؤلفون: | Machulkin AE; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, 450054 Ufa, Russian Federation. Electronic address: alekseymachulkin@rambler.ru., Skvortsov DA; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation. Electronic address: skvorratd@mail.ru., Ivanenkov YA; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation; National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation; ChemDiv, San Diego, CA, USA; Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, 450054 Ufa, Russian Federation., Ber AP; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Kavalchuk MV; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Aladinskaya AV; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation., Uspenskaya AA; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Shafikov RR; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Plotnikova EA; P. A. Herzen Moscow Oncology Research Institute, 3, 2th Botkinsky Driveway, Moscow 125284, Russian Federation., Yakubovskaya RI; P. A. Herzen Moscow Oncology Research Institute, 3, 2th Botkinsky Driveway, Moscow 125284, Russian Federation., Nimenko EA; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Zyk NU; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Beloglazkina EK; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Zyk NV; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Koteliansky VE; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Majouga AG; Lomonosov Moscow State University, Chemistry Dept., Leninskie gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation; National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation; Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian Federation. |
| المصدر: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Aug 15; Vol. 29 (16), pp. 2229-2235. Date of Electronic Publication: 2019 Jun 20. |
| نوع المنشور: | Letter; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3405 (Electronic) Linking ISSN: 0960894X NLM ISO Abbreviation: Bioorg Med Chem Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1991- |
| مواضيع طبية MeSH: | Drug Delivery Systems/*methods , Paclitaxel/*chemical synthesis , Prostatic Neoplasms/*drug therapy, Animals ; Humans ; Male ; Mice |
| مستخلص: | Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC. (Copyright © 2019 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Drug delivery; Paclitaxel; Prostate cancer; Prostate-specific membrane antigen |
| المشرفين على المادة: | P88XT4IS4D (Paclitaxel) |
| تواريخ الأحداث: | Date Created: 20190629 Date Completed: 20200917 Latest Revision: 20200917 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.bmcl.2019.06.035 |
| PMID: | 31248772 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3405 |
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| DOI: | 10.1016/j.bmcl.2019.06.035 |