Inhibition of Fungal Sphingolipid Biosynthesis by Rustmicin, Galbonolide B and Their New 21-Hydroxy Analogs.

Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids.

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“…In the context of IPCs, aureobasidin, khafrefungin and galbonolide are known as IPC inhibitors [106][107][108][109].…”

Section: Sphingolipids As Targets For Treatment Of Fungal Infections mentioning

confidence: 99%

Sphingolipids as Targets for Treatment of Fungal Infections

et al. 2016

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“…7), isolated from Micromonospora species are also the inhibitors of IPC synthase along with their various other analogues [132][133][134]. Rustmicin 48 exhibits potent activity against IPC synthase of C. neoformans (IC 50 = 70 pM) and C. albicans (IC 50 = 3.8 nM), though it is less active in mouse model of cryptococcosis than predicted from its in vitro activity [135,136].…”

Section: Sulfate Assimilation (Sa) Pathwaymentioning

confidence: 92%

Current Advances in Antifungal Targets and Drug Development

Sundriyal¹,

Sharma²,

Jain

2006

CMC

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Fungi are one of the most neglected pathogens apparent from the fact that the Amphotericin B, a polyene antibiotic, discovered way back in 1956 is still used as a 'gold standard' for antifungal therapy. Past two decades have witnessed a dramatic rise in the incidences of life threatening systemic fungal infections. This can be ascribed to the increase in the number of immuno-compromised patients due to rise in HIV infected population, cancer chemotherapy and indiscriminate use of antibiotics. Majority of clinically used antifungals suffer from various drawbacks in terms of toxicity, efficacy and cost, and their frequent use has led to the emergence of resistant strains. Hence, there is a great demand for novel antifungals belonging to wide range of structural classes, selectively acting on novel targets with fewer side effects. This article aims at reviewing recent efforts made towards discovering novel antifungal drug targets and investigational molecules acting on them.

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“…Several compounds, such as aureobasidin, khafrefungin and rustmicin, have been discovered to inhibit Ipc1 activity [80,[112][113][114][115] with no affect on mammalian SMS activity in vitro (Del Poeta, unpublished results). Aureobasidin and rustmicin (Fig.…”

Section: The Sphingolipid Pathway In Fungimentioning

confidence: 96%

Sphingolipids as Targets for Microbial Infections

McQuiston¹,

Haller²,

Poeta³

2006

MRMC

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Sphingolipids had long been regarded as merely structural components of eukaryotic cellular membranes. Research has discovered sphingolipids to have crucial roles in cellular processes as bioactive molecules. Lately, there has also been an increased interest in sphingolipids and sphingolipid-metabolizing enzymes as mediators of microbial pathogenicity and as potential targets for the development of new therapeutics. This minireview will provide a comprehensive analysis of sphingolipid pathways in mammalian and microbial cells, highlighting their uniqueness and discussing their potential as therapeutic targets for microbial infections.

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Inhibition of Fungal Sphingolipid Biosynthesis by Rustmicin, Galbonolide B and Their New 21-Hydroxy Analogs.

Cited by 38 publications

References 20 publications

Sphingolipids as Targets for Treatment of Fungal Infections

Sphingolipids as Targets for Treatment of Fungal Infections

Current Advances in Antifungal Targets and Drug Development

Sphingolipids as Targets for Microbial Infections

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