Discovery and synthesis of 3- and 21-substituted fusidic acid derivatives as reversal agents of P-glycoprotein-mediated multidrug resistance

Guo, Mengye; Ren, Qianwen; Wang, Binghua; Ji, Wentao; Ni, Jingxuan; Ya-qi, Feng; Bi, Yi; Tian, Jingwei; Wang, Hongbo

doi:10.1016/j.ejmech.2019.111668

Cited by 12 publications

(3 citation statements)

References 21 publications

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“…Further studies revealed that the combination of derivative 29 with paclitaxel re-sensitized the multidrug-resistant oral epidermoid carcinoma (KBV) cell line to paclitaxel. A mechanism study found that compound 29 enhanced the ATPase activity of P-glycoprotein (P-gp) by inhibiting the drug pump activity of P-gp, but did not affect the expression of P-gp (Guo et al, 2019).…”

Section: Tumor Multidrug Resistance Reversal Activitymentioning

confidence: 99%

“…FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial (Godtfredsen W. O. et al, 1962), antiparasitic (Gupta et al, 2013;Salama et al, 2013), antituberculosis (Cicek-Saydam et al, 2001), anticancer (Ni et al, 2019), tumor multidrug resistance (MDR) reversal (Guo et al, 2019), anti-inflammation (Kilic et al, 2002), antifungal (Bi et al, 2020), and antiviral activity (Liu et al, 2019) in vivo and in vitro. However, there is no review on the semisynthesis, biological activities, and structure-activity relationship (SAR) studies of FA derivatives in the last 2 decades.…”

Section: Introductionmentioning

confidence: 99%

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Bioactivities and Structure–Activity Relationships of Fusidic Acid Derivatives: A Review

Long

Zhang

et al. 2021

Front. Pharmacol.

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Fusidic acid (FA) is a natural tetracyclic triterpene isolated from fungi, which is clinically used for systemic and local staphylococcal infections, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections. FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial, antimalarial, antituberculosis, anticancer, tumor multidrug resistance reversal, anti-inflammation, antifungal, and antiviral activity in vivo and in vitro. The semisynthesis, structural modification and biological activities of FA derivatives have been extensively studied in recent years. This review summarized the biological activities and structure–activity relationship (SAR) of FA in the last two decades. This summary can prove useful information for drug exploration of FA derivatives.

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Section: Tumor Multidrug Resistance Reversal Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioactivities and Structure–Activity Relationships of Fusidic Acid Derivatives: A Review

Long

Zhang

et al. 2021

Front. Pharmacol.

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“…Moreover, a significant place in the inventory of biologically active molecules, including those exhibiting an antibacterial effect, is occupied by nitrogen-containing derivatives [ 14 ]. Previously, it was shown that the synthesis of N-substituted analogues is a promising trend in the chemical modifications of fusidic acid [ 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

3-Amino-Substituted Analogues of Fusidic Acid as Membrane-Active Antibacterial Compounds

et al. 2023

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Fusidic acid (FA) is an antibiotic with high activity against Staphylococcus aureus; it has been used in clinical practice since the 1960s. However, the narrow antimicrobial spectrum of FA limits its application in the treatment of bacterial infections. In this regard, this work aims both at the study of the antimicrobial effect of a number of FA amines and at the identification of their potential biological targets. In this way, FA analogues containing aliphatic and aromatic amino groups and biogenic polyamine, spermine and spermidine, moieties at the C-3 atom, were synthesized (20 examples). Pyrazinecarboxamide-substituted analogues exhibit a high antibacterial activity against S. aureus (MRSA) with MIC ≤ 0.25 μg/mL. Spermine and spermidine derivatives, along with activity against S. aureus, also inhibit the growth and reproduction of Gram-negative bacteria Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa, and have a high fungicidal effect against Candida albicans and Cryptococcus neoformans. The study of the membrane activity demonstrated that the spermidine- and spermine-containing compounds are able to immerse into membranes and disorder the lipidsleading to a detergent effect. Moreover, spermine-based compounds are also able to form ion-permeable pores in the lipid bilayers mimicking the bacterial membranes. Using molecular docking, inhibition of the protein synthesis elongation factor EF-G was proposed, and polyamine substituents were shown to make the greatest contribution to the stability of the complexes of fusidic acid derivatives with biological targets. This suggests that the antibacterial effect of the obtained compounds may be associated with both membrane activity and inhibition of the elongation factor EF-G.

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Indole Derivatives of Fusidane Triterpenoids: Synthesis and the Antibacterial Activity

Салимова

Magafurova

Tret’yakova

et al. 2020

Chem Heterocycl Comp

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Discovery and synthesis of 3- and 21-substituted fusidic acid derivatives as reversal agents of P-glycoprotein-mediated multidrug resistance

Cited by 12 publications

References 21 publications

Bioactivities and Structure–Activity Relationships of Fusidic Acid Derivatives: A Review

Bioactivities and Structure–Activity Relationships of Fusidic Acid Derivatives: A Review

3-Amino-Substituted Analogues of Fusidic Acid as Membrane-Active Antibacterial Compounds

Indole Derivatives of Fusidane Triterpenoids: Synthesis and the Antibacterial Activity

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