دورية أكاديمية
Semisynthetic Amides of Polyene Antibiotic Natamycin.
| العنوان: | Semisynthetic Amides of Polyene Antibiotic Natamycin. |
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| المؤلفون: | Tevyashova AN; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Efimova SS; Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg194064, Russia., Alexandrov AI; Federal Research Center 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Bach Institute of Biochemistry, 33 Leninsky Avenue, Bld. 2, Moscow119071, Russia., Ghazy ESMO; Federal Research Center 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Bach Institute of Biochemistry, 33 Leninsky Avenue, Bld. 2, Moscow119071, Russia.; Institute of Biochemical Technology and Nanotechnology, Peoples' Friendship University of Russia (RUDN), 6 Miklukho-Maklaya Street, Moscow117198, Russia.; Department of Microbiology, Faculty of Pharmacy, Tanta University, Tanta31111, Egypt., Bychkova EN; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Solovieva SE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Zatonsky GB; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Grammatikova NE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Dezhenkova LG; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Pereverzeva ER; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Isakova EB; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Ostroumova OS; Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Avenue, St. Petersburg194064, Russia., Omelchuk OA; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia., Muravieva VV; National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparin Street, Moscow117997, Russia., Krotova MM; National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparin Street, Moscow117997, Russia., Priputnevich TV; National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparin Street, Moscow117997, Russia., Shchekotikhin AE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya, Moscow119021, Russia. |
| المصدر: | ACS infectious diseases [ACS Infect Dis] 2023 Jan 13; Vol. 9 (1), pp. 42-55. Date of Electronic Publication: 2022 Dec 23. |
| 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: | Natamycin*/pharmacology , Mycoses*/drug therapy, Animals ; Mice ; Humans ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; HEK293 Cells ; Polyenes/pharmacology ; Candida ; Saccharomyces cerevisiae ; Mammals |
| مستخلص: | Natamycin is a macrolide polyene antibiotic, characterized by a potent broad spectrum antifungal activity and low toxicity. However, it is not used for the treatment of systemic mycoses due to its low bioavailability and low solubility in aqueous solutions. In order to create new semisynthetic antifungal agents for treatment of mycoses, a series of water-soluble amides of natamycin were synthesized. Antifungal activities of natamycin derivatives were investigated against Candida spp. , including a panel of Candida auris clinical isolates and filamentous fungi. Toxicity for mammalian cells was assayed by monitoring antiproliferative activity against human postnatal fibroblasts (HPF) and human embryonic kidney cells (HEK293). By comparing leakage of contents from ergosterol versus cholesterol containing vesicles, a ratio that characterizes the efficacy and safety of natamycin and its derivatives was determined (EI, efficiency index). Ability of all tested semisynthetic natamycines to prevent proliferation of the yeast Candida spp. cells was comparable or even slightly higher to those of parent antibiotic. Interestingly, amide 8 was more potent than natamycin ( 1 ) against all tested C. auris strains (MIC values 2 μg/mL vs 8 μg/mL, respectively). Among 7 derivatives, amide 10 with long lipophilic side chains showed the highest EI and strong antifungal activity in vitro but was more toxic against HPF. In vivo experiments with amide 8 showed in vivo efficacy on a mouse candidemia model with a larger LD |
| فهرسة مساهمة: | Keywords: Natamycin; amides; antifungal activity; calcein leakage; polyene antibiotics; semisynthetic derivatives; unilamellar vesicles; water-solubility |
| المشرفين على المادة: | 8O0C852CPO (Natamycin) 0 (Antifungal Agents) 0 (Anti-Bacterial Agents) 0 (Polyenes) |
| تواريخ الأحداث: | Date Created: 20221223 Date Completed: 20230116 Latest Revision: 20230210 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1021/acsinfecdis.2c00237 |
| PMID: | 36563312 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2373-8227 |
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| DOI: | 10.1021/acsinfecdis.2c00237 |