The Need for New Antifungal Drugs

Clark, Alice M.

doi:10.1007/978-1-4899-6729-9_1

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…235,236 However, because of their potential liver toxicity, these compounds have not been approved through clinical trials. 235,237,238 Microvirin, a cyanobacterial monovalent lectin, exerts potent activity against HIV-1 infection (IC 50 = 2−12 nM) by targeting the Man-α-(1−2)-Man fragment of the high-mannose-type oligosaccharides of the gp120 viral protein. 239 However, the challenges of microvirin for clinical use include large scale production and demonstrating low toxicity, mitogenicity, and immunogenicity.…”

Section: ■ Rigid Noncovalent Synthetic Carbohydrate Receptorsmentioning

confidence: 99%

“…The abundance of the GlcNAc 2 Man 3 core and mannosides on the terminal sugars of the glycan shield of several infectious diseases such as HIV, HCV, and others has made these glycans an important target for CBAs. For example, pradimicin A and the benanomicin A antibiotics, which bind to the terminal mannosides on the fungal membrane, ,, have antiviral activity against HIV-1, with IC 50 values in the micromolar range. , However, because of their potential liver toxicity, these compounds have not been approved through clinical trials. ,, Microvirin, a cyanobacterial monovalent lectin, exerts potent activity against HIV-1 infection (IC 50 = 2–12 nM) by targeting the Man-α-(1–2)-Man fragment of the high-mannose-type oligosaccharides of the gp120 viral protein . However, the challenges of microvirin for clinical use include large scale production and demonstrating low toxicity, mitogenicity, and immunogenicity.…”

Section: Antiviral Activity Of Synthetic Carbohydrate Receptorsmentioning

confidence: 99%

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Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment

et al. 2020

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Carbohydrate–receptor interactions are often involved in the docking of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs), small molecules that bind carbohydrates, could bring carbohydrate–receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate–receptor interactions in viral infection, the evolution of SCRs, and recent results demonstrating their ability to prevent viral infections in vitro. Common SCR design strategies based on boronic ester formation, metal chelation, and noncovalent interactions are discussed. The benefits of incorporating the idiosyncrasies of natural glycan-binding proteinsincluding flexibility, cooperativity, and multivalencyinto SCR design to achieve nonglucosidic specificity are shown. These studies into SCR design and binding could lead to new strategies for mitigating the grave threat to human health posed by enveloped viruses, which are heavily glycosylated viroids that are the cause of some of the most pressing and untreatable diseases, including HIV, Dengue, Zika, influenza, and SARS-CoV-2.

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Section: ■ Rigid Noncovalent Synthetic Carbohydrate Receptorsmentioning

confidence: 99%

Section: Antiviral Activity Of Synthetic Carbohydrate Receptorsmentioning

confidence: 99%

Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment

et al. 2020

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“…Ähnlich wie bei anderen Medikamenten sollen auch pflanzliche Präparate zukünftig nur zugelassen werden, nachdem ihre Sicherheit, ihre Effektivität und Qualität nachgewiesen ist (Grünwald, 1998 Von den höheren Pflanzen sind bisher nur 5-15% auf mögliche bioaktive Stoffe hin untersucht worden (Balandrin et al, 1993 (Wani et al, 1971 Stierle et al (1993Stierle et al ( , 1995 (Strobel et al, 1996). (Clark, 1992;Odds, 1995 sind weitere gefolgt (Sato et al, 1978 (Plän, 1999). Auch wenn sich eine biologische Lösung nur selten direkt übernehmen läßt, so kann sie entscheidende Impulse geben und damit zu neuen Lösungen führen (Nachtigall, 1998 (Miller et al, 1995 (Vandermeer, 1989).…”

Section: Anwendungsbereich Der Schutzmechanismen Des Protokollsunclassified

Erhaltung und nachhaltige Nutzung der Biosphäre

2000

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“…The need for new drugs to treat systemic fungal infections has intensified due to the increase in the immunocompromised-patient population . The echinocandins are a class of fungicidal cell-wall active lipopeptides that are specific inhibitors of β-(1,3)- d -glucan synthesis …”

Section: Introductionmentioning

confidence: 99%

Semisynthesis of an Antifungal Lipopeptide Echinocandin

et al. 1999

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Compound 1 is a macrocyclic lipopeptide belonging to the echinocandin family, which has been effective in treating systemic fungal infections. In this paper, we report a unique regio-, chemo-, and stereoselective synthesis of 1 in four steps from the deacylated nucleus 3 in an impressive 83% overall yield. Highlights of this synthesis include a selective reduction of the amide to the amine and a highly stereoselective (99:1 α/β) introduction of the 2-aminoethyl hemiaminal. In addition, the synthesis of the naphthoyl side chain was accomplished in three steps in 79% overall isolated yield from commercially available 6-bromo-2-naphthol.

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The Need for New Antifungal Drugs

Cited by 12 publications

References 48 publications

Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment

Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment

Erhaltung und nachhaltige Nutzung der Biosphäre

Semisynthesis of an Antifungal Lipopeptide Echinocandin

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