Metronidazole citrate ester as the new prodrug of metronidazole
Many attempts have been made since 1960th to obtain ester prodrugs of metronidazole active moiety to be used for parenteral forms, with the same action against microorganisms. Until now there is not any ester prodrug marketed for this route of administration. The synthesis from metronidazole and cit...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Growing Science
2017-07-01
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| Series: | Current Chemistry Letters |
| Subjects: | |
| Online Access: | http://www.growingscience.com/ccl/Vol6/ccl_2017_10.pdf |
| _version_ | 1811279437059063808 |
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| author | Elżbieta Dąbrowska-Maś Wojciech Raś |
| author_facet | Elżbieta Dąbrowska-Maś Wojciech Raś |
| author_sort | Elżbieta Dąbrowska-Maś |
| collection | DOAJ |
| description | Many attempts have been made since 1960th to obtain ester prodrugs of metronidazole active moiety to be used for parenteral forms, with the same action against microorganisms. Until now there is not any ester prodrug marketed for this route of administration. The synthesis from metronidazole and citric acid of new ester prodrug of metronidazole with citric acid in a form of disodium salt and the way of purification were described. The structure of sodium metronidazole citrate was elucidated with IR, MS, 1H NMR and 13C NMR spectra. Also impurities present in this ester were identified using 1H NMR technique. Additionally, the solubility in water was measured as well as pH of 10% (w/w) aqueous solution, and both values indicated that there is a possibility to obtain concentrated solutions for injection of neutral pH, even without need of buffering. Finally, the Ames assay using six tester strains S. typhimurium TA98, TA100, TA1535, TA1537 and E. coli uvrA, [pKM101] shown weak genotoxic potential, comparable with metronidazole. |
| first_indexed | 2024-04-13T00:55:45Z |
| format | Article |
| id | doaj.art-a9ba30b8e5d24755b0b8749b1431d058 |
| institution | Directory Open Access Journal |
| issn | 1927-7296 1927-730X |
| language | English |
| last_indexed | 2024-04-13T00:55:45Z |
| publishDate | 2017-07-01 |
| publisher | Growing Science |
| record_format | Article |
| series | Current Chemistry Letters |
| spelling | doaj.art-a9ba30b8e5d24755b0b8749b1431d0582022-12-22T03:09:43ZengGrowing ScienceCurrent Chemistry Letters1927-72961927-730X2017-07-016416717610.5267/j.ccl.2017.6.002Metronidazole citrate ester as the new prodrug of metronidazoleElżbieta Dąbrowska-MaśWojciech RaśMany attempts have been made since 1960th to obtain ester prodrugs of metronidazole active moiety to be used for parenteral forms, with the same action against microorganisms. Until now there is not any ester prodrug marketed for this route of administration. The synthesis from metronidazole and citric acid of new ester prodrug of metronidazole with citric acid in a form of disodium salt and the way of purification were described. The structure of sodium metronidazole citrate was elucidated with IR, MS, 1H NMR and 13C NMR spectra. Also impurities present in this ester were identified using 1H NMR technique. Additionally, the solubility in water was measured as well as pH of 10% (w/w) aqueous solution, and both values indicated that there is a possibility to obtain concentrated solutions for injection of neutral pH, even without need of buffering. Finally, the Ames assay using six tester strains S. typhimurium TA98, TA100, TA1535, TA1537 and E. coli uvrA, [pKM101] shown weak genotoxic potential, comparable with metronidazole.http://www.growingscience.com/ccl/Vol6/ccl_2017_10.pdfAmes assayEster of metronidazoleImpurity profileMetronidazole citrate disodiumMetronidazole prodrug |
| spellingShingle | Elżbieta Dąbrowska-Maś Wojciech Raś Metronidazole citrate ester as the new prodrug of metronidazole Current Chemistry Letters Ames assay Ester of metronidazole Impurity profile Metronidazole citrate disodium Metronidazole prodrug |
| title | Metronidazole citrate ester as the new prodrug of metronidazole |
| title_full | Metronidazole citrate ester as the new prodrug of metronidazole |
| title_fullStr | Metronidazole citrate ester as the new prodrug of metronidazole |
| title_full_unstemmed | Metronidazole citrate ester as the new prodrug of metronidazole |
| title_short | Metronidazole citrate ester as the new prodrug of metronidazole |
| title_sort | metronidazole citrate ester as the new prodrug of metronidazole |
| topic | Ames assay Ester of metronidazole Impurity profile Metronidazole citrate disodium Metronidazole prodrug |
| url | http://www.growingscience.com/ccl/Vol6/ccl_2017_10.pdf |
| work_keys_str_mv | AT elzbietadabrowskamas metronidazolecitrateesterasthenewprodrugofmetronidazole AT wojciechras metronidazolecitrateesterasthenewprodrugofmetronidazole |