Conjugation of amino-containing drugs to polysaccharides by tosylation: Amphotericin B-arabinogalactan conjugates

Tirsta Ehrenfreund-Kleinman; Jacob Golenser; Abraham J. Domb

doi:10.1016/j.biomaterials.2003.09.080

Conjugation of amino-containing drugs to polysaccharides by tosylation: Amphotericin B-arabinogalactan conjugates

Tirsta Ehrenfreund-Kleinman, Jacob Golenser, Abraham J. Domb^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond. AG-AmB conjugates were soluble in water and exhibited improved stability in aqueous solutions as compared to the unbound drug. The conjugates showed comparable inhibitory concentration values against the pathogenic yeast Candida albicans, and against Leishmania major parasites. They were about 60 times less hemolytic against sheep erythrocytes than the free drug, and less toxic when injected i.v. to BALB/c mice.

Original language	English
Pages (from-to)	3049-3057
Number of pages	9
Journal	Biomaterials
Volume	25
Issue number	15
DOIs	https://doi.org/10.1016/j.biomaterials.2003.09.080
State	Published - Jul 2004

Keywords

Amphotericin-B
Arabinogalactan
Mesylate
Tosylate
Water-soluble conjugate

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10.1016/j.biomaterials.2003.09.080

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title = "Conjugation of amino-containing drugs to polysaccharides by tosylation: Amphotericin B-arabinogalactan conjugates",

abstract = "The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond. AG-AmB conjugates were soluble in water and exhibited improved stability in aqueous solutions as compared to the unbound drug. The conjugates showed comparable inhibitory concentration values against the pathogenic yeast Candida albicans, and against Leishmania major parasites. They were about 60 times less hemolytic against sheep erythrocytes than the free drug, and less toxic when injected i.v. to BALB/c mice.",

keywords = "Amphotericin-B, Arabinogalactan, Mesylate, Tosylate, Water-soluble conjugate",

author = "Tirsta Ehrenfreund-Kleinman and Jacob Golenser and Domb, {Abraham J.}",

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AU - Golenser, Jacob

AU - Domb, Abraham J.

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N2 - The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond. AG-AmB conjugates were soluble in water and exhibited improved stability in aqueous solutions as compared to the unbound drug. The conjugates showed comparable inhibitory concentration values against the pathogenic yeast Candida albicans, and against Leishmania major parasites. They were about 60 times less hemolytic against sheep erythrocytes than the free drug, and less toxic when injected i.v. to BALB/c mice.

AB - The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond. AG-AmB conjugates were soluble in water and exhibited improved stability in aqueous solutions as compared to the unbound drug. The conjugates showed comparable inhibitory concentration values against the pathogenic yeast Candida albicans, and against Leishmania major parasites. They were about 60 times less hemolytic against sheep erythrocytes than the free drug, and less toxic when injected i.v. to BALB/c mice.

KW - Amphotericin-B

KW - Arabinogalactan

KW - Mesylate

KW - Tosylate

KW - Water-soluble conjugate

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JO - Biomaterials

JF - Biomaterials

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ER -

Conjugation of amino-containing drugs to polysaccharides by tosylation: Amphotericin B-arabinogalactan conjugates

Abstract

Keywords

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