Scalable and cost-effective tosylation-mediated synthesis of antifungal and fungal diagnostic 6â³-Modified amphiphilic kanamycins.
Eur J Med Chem
; 182: 111639, 2019 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-31470306
ABSTRACT
Amphiphilic kanamycins bearing hydrophobic modifications at the 6â³ position have attracted interest due to remarkable antibacterial-to-antifungal switches in bioactivity. In this report, we investigate a hurdle that hinders practical applications of these amphiphilic kanamycins a cost-effective synthesis that allows the incorporation of various connecting functionalities to which the hydrophobic moieties are connected to the kanamycin core. A cost-effective tosylation enables various modifications at the 6â³ position, which is scalable to a 90-g scale. The connecting functionalities, such as amine and thiol, were not the dominant factor for biological activity. Instead, the linear chain length played the decisive role. Amphiphilic kanamycin attached with tetradecyl (C14) or hexadecyl (C16) showed strong antifungal and modest antibacterial activities than with shorter chains (C6-C10). However, increases in chain length were closely correlated with an increase in HeLa cell toxicity. Thus, a compromise between the antimicrobial activities and cytotoxicities, for optimal efficacy of amphiphilic kanamycins may contain chain lengths between C8 and C12. Finally, the described synthetic protocol also allows the preparation of a fluorescent amphiphilic kanamycin selective toward fungi.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tensoativos
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Bactérias
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Canamicina
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Fungos
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Antibacterianos
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Antifúngicos
Tipo de estudo:
Diagnostic_studies
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Guideline
/
Health_economic_evaluation
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos