دورية أكاديمية
Discovery of Amphamide, a Drug Candidate for the Second Generation of Polyene Antibiotics.
| العنوان: | Discovery of Amphamide, a Drug Candidate for the Second Generation of Polyene Antibiotics. |
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| المؤلفون: | Tevyashova AN; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia.; D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya sq., Moscow, 125047, Russia., Bychkova EN; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Solovieva SE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Zatonsky GV; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Grammatikova NE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Isakova EB; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Mirchink EP; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Treshchalin ID; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Pereverzeva ER; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Bykov EE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia., Efimova SS; Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky ave., St. Petersburg, 194064, Russia., Ostroumova OS; Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky ave., St. Petersburg, 194064, Russia., Shchekotikhin AE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow, 199021, Russia.; D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya sq., Moscow, 125047, Russia. |
| المصدر: | ACS infectious diseases [ACS Infect Dis] 2020 Aug 14; Vol. 6 (8), pp. 2029-2044. Date of Electronic Publication: 2020 Jul 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: ACS Publications Country of Publication: United States NLM ID: 101654580 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-8227 (Electronic) Linking ISSN: 23738227 NLM ISO Abbreviation: ACS Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ACS Publications, [2015]- |
| مواضيع طبية MeSH: | Anti-Bacterial Agents*/pharmacology , Pharmaceutical Preparations*, Amphotericin B/pharmacology ; Animals ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Mice ; Polyenes/pharmacology ; Prospective Studies |
| مستخلص: | Amphotericin B (AmB, 1 ) is the drug of choice for treating the most serious systemic fungal or protozoan infections. Nevertheless, its application is limited by low solubility in aqueous media and serious side effects such as infusion-related reactions, hemolytic toxicity, and nephrotoxicity. Owing to these limitations, it is essential to search for the polyene derivatives with better chemotherapeutic properties. With the objective of obtaining AmB derivatives with lower self-aggregation and improved solubility, we synthesized a series of amides of AmB bearing an additional basic group in the introduced residue. The screening of antifungal activity in vitro revealed that N -(2-aminoethyl)amide of AmB (amphamide, 6 ) had superior antifungal activity compared to that of the paternal AmB. Preclinical studies in mice confirmed that compound 6 had a much lower acute toxicity and higher antifungal efficacy in the model of mice candidosis sepsis compared with that of AmB ( 1 ). Thus, the discovered amphamide is a promising drug candidate for the second generation of polyene antibiotics and is also prospective for in-depth preclinical and clinical evaluation. |
| فهرسة مساهمة: | Keywords: acute toxicity; amphotericin B; antifungal activity; in vivo antifungal efficacy; mechanism of action; polyene antibiotics |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) 0 (Antifungal Agents) 0 (Pharmaceutical Preparations) 0 (Polyenes) 7XU7A7DROE (Amphotericin B) |
| تواريخ الأحداث: | Date Created: 20200630 Date Completed: 20210623 Latest Revision: 20210623 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1021/acsinfecdis.0c00068 |
| PMID: | 32598131 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2373-8227 |
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| DOI: | 10.1021/acsinfecdis.0c00068 |