A Stability-Indicating RP-HPLC-UV method for determination of fidaxomicin and its hydrolytic degradation products

Kumar, K. Vinod; Sharma, H. R.; Peraman, Ramalingam; Pudipatla, SarvaSree

doi:10.1007/s13738-021-02343-4

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…Fdx was reported to be stable in a pH range of 4–6 . At lower pH, acidic degradation renders the molecule instable. ,, With the increased stability of our S-glycosidic analogue toward acid-mediated nucleophilic substitution, we next wanted to study the effect of exposure to acidic conditions as they are encountered in gastric fluid. Despite the poor water solubility of Fdx, the solubility and thus the exposure to the acidic conditions are significantly impacted by the presence of solubility enhancers.…”

Section: Resultsmentioning

confidence: 99%

“…17 At lower pH, acidic degradation renders the molecule instable. 17,18,50 With the increased stability of our S-glycosidic analogue toward acid-mediated nucleophilic substitution, we next wanted to study the effect of exposure to acidic conditions as they are encountered in gastric fluid. Despite the poor water solubility of Fdx, 17 Dificlir, Fdx is supplied along with microcrystalline cellulose and sodium starch glycollate, 9 which can enhance the solubility or dissolution rate.…”

Section: Acidic Degradation and Its Impact On Antibacterial Activitymentioning

confidence: 99%

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Formal Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Ferrara,

Chesnokov,

Dittmann

et al. 2024

JACS Au

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Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is approved only for Clostridioides difficile infections. Poor water solubility and acid lability preclude its use for other infections. Herein, we describe our strategy to overcome the acid lability by introducing acid-stable S-linked glycosides. We describe the direct, diastereoselective modification of unprotected Fdx without the need to avoid air or moisture. Using our newly established approach, Fdx was converted to the single atom exchanged analogue S-Fdx, in which the acid labile O-glycosidic bond to the noviose sugar was replaced by the acid stable S-glycosidic bond. Studies of the antibacterial activity of a structurally diverse set of thioglycoside derivatives revealed high potency of acyl derivatives of S-Fdx against Clostridioides difficile (MIC range: 0.12–4 μg/mL) and excellent potency against Clostridium perfringens (MIC range: 0.06–0.5 μg/mL).

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Section: Resultsmentioning

confidence: 99%

Section: Acidic Degradation and Its Impact On Antibacterial Activitymentioning

confidence: 99%

Formal Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Ferrara,

Chesnokov,

Dittmann

et al. 2024

JACS Au

View full text Add to dashboard Cite

show abstract

“…17 At lower pH, acidic degradation renders the molecule instable. 17,18,47 With the increased stability of our S-glycosidic analogue towards acid-mediated nucleophilic substitution, we next wanted to study the effect of exposure to acidic conditions as they are encountered in gastric fluid. Despite the poor water solubility of Fdx, 17 the solubility and thus, the exposure to the acidic conditions are significantly impacted by the presence of solubility enhancers.…”

Section: Acidic Degradation and Its Impact On Antibacterial Activitymentioning

confidence: 99%

Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Ferrara,

Chesnokov,

Dittmann

et al. 2024

Preprint

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Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is only approved for Clostridioides difficile infections. Poor water solubility and acid lability preclude its use for other infections. Herein, we describe our strategy to overcome the acid lability by introducing acid stable S-linked glycosides. We describe the direct, diastereoselective modification of unprotected Fdx without the need to avoid air or moisture. Using our newly established approach, Fdx was converted to the single atom exchanged analogue S-Fdx, in which the acid labile O-glycosidic bond to the noviose sugar is replaced by the acid stable S-glycosidic bond. Studies of the antibacterial activity of a structurally diverse set of thioglycoside derivatives revealed high potency of acyl derivatives of S-Fdx against Clostridioides difficile (MIC range: 0.12–4 μg/mL) and excellent potency against Clostridium perfringens (MIC range: 0.06–0.5 μg/mL).

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Nuclear Magnetic Resonance Spectroscopy for Quantitative Analysis: A Review for Its Application in the Chemical, Pharmaceutical and Medicinal Domains

Khalil

Kashif

2021

Critical Reviews in Analytical Chemistry

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A Stability-Indicating RP-HPLC-UV method for determination of fidaxomicin and its hydrolytic degradation products

Cited by 3 publications

References 15 publications

Formal Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Formal Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity

Nuclear Magnetic Resonance Spectroscopy for Quantitative Analysis: A Review for Its Application in the Chemical, Pharmaceutical and Medicinal Domains

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