The Substantial Improvement of Amphotericin B Selective Toxicity Upon Modification of Mycosamine with Bulky Substituents - Publikacja - MOST Wiedzy

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The Substantial Improvement of Amphotericin B Selective Toxicity Upon Modification of Mycosamine with Bulky Substituents

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Abstract: Background: It is assumed that the unfavorable selective toxicity of an antifungal drug Amphotericin B (AmB) can be improved upon chemical modification of the antibiotic molecule. Objective: The aim of this study was verification of the hypothesis that introduction of bulky substituents at the amino sugar moiety of the antibiotic may result in diminishment of mammalian vitro toxicity of thus prepared AmB derivatives. Methods: Twenty-eight derivatives of AmB were obtained upon chemical modification of amino group of mycosamine residue. This set comprised 10 N-succinimidyl-, 4 N-benzyl-, 5 Nthioureidyl- and 9 N-aminoacyl derivatives. Parameters characterizing biological in vitro activity of novel compounds were determined. Results: All the novel compounds demonstrated lower than AmB antifungal in vitro activity but most of them exhibited negligible cytotoxicity against human erythrocytes and three mammalian cell lines. In consequence, the selective toxicity of majority of novel antifungals, reflected by the selective toxicity index (STI = EH50/IC50) was improved in comparison with that of AmB, especially in the case of 5 compounds. The novel AmB derivatives with the highest STI, induced substantial potassium efflux from Candida albicans cells at concentrations slightly lower than IC50s but did not trigger potassium release from human erythrocytes at concentrations lower than 100 μg/mL. Conclusion: Some of the novel AmB derivatives can be considered promising antifungal drug candidates.

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
Medicinal Chemistry nr 16, strony 128 - 139,
ISSN: 1573-4064
Język:
angielski
Rok wydania:
2020
Opis bibliograficzny:
Borowski E., Salewska N., Boros-Majewska J., Serocki M., Chabowska I., Milewska M., Ziętkowski D., Milewski S.: The Substantial Improvement of Amphotericin B Selective Toxicity Upon Modification of Mycosamine with Bulky Substituents// Medicinal Chemistry -Vol. 16,iss. 1 (2020), s.128-139
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.2174/1573406415666181203114629
Weryfikacja:
Politechnika Gdańska

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