WF11899A, B and C, novel antifungal lipopeptides. II. Biological properties.

Self Cite

Micafungin is the second approved antifungal agent in the echinocandin series and is now used worldwide in chemotherapy for life-threatening fungal infections. It is water-soluble and is semi-synthesized from the acylated cyclic hexapeptide FR901379, a natural product from the fungus Coleophoma empetri F-11899, through enzymatic deacylation of FR901379, followed by chemical reacylation with the optimized N-acyl side chain. The water solubility of micafungin is ascribed to a sulfate moiety in the molecule. This feature differentiates micafungin from other echinocandin members. Micafungin is a potent inhibitor of 1,3-b-glucan synthase, an enzyme necessary for cell-wall synthesis of several fungal pathogens. The Journal of Antibiotics (2009) and Cryptococcus neoformans are a threat to human health. Incidences of these systemic fungal infections have increased significantly over the past few years. The major reasons for this dramatic increase are the extensive use of broad-spectrum antibiotics and the growing number of immunocompromised patients with acquired immunodeficiency syndrome (AIDS), cancer and transplants. 1,2 In the mid 1900s, few compounds, such as polyenes (for example, nystatin and amphotericin B) and flucytosine, were available for antifungal chemotherapy. Although the development of azole drugs started in the early 1970s, only a limited number of antifungal agents were available for treatment of life-threatening fungal infections. Moreover, the existing agents had disadvantages, such as the significant nephrotoxicity of amphotericin B 3 and the emergence of resistance to the azoles. 4 To overcome these defects, lipid formulations of polyenes were developed to reduce toxicity, and new triazoles (for example, voriconazole, ravuconazole and posaconazole) were developed to improve the antifungal spectra or susceptibility to azoleresistant isolates. 5 Despite a number of therapeutic advancements, there was a need to develop a new class of antifungal agents with novel mechanisms of action.

Section: Discovery Of Fr901379mentioning

confidence: 99%

Micafungin: a sulfated echinocandin

Hashimoto

2009

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“…These compounds have similar structures to FR901379 [3,4], the points of difference having different amino acid constituents compared to FR901379 and, most strikingly, a sulphate residue presenting at a different position of the aryl ring. Other related antifungal lipopeptides of fungal origin are FR901379 [3,4], echinocandin B [5] aculeacins [6], mulundocandin [7] and pneumocandins [8,9], which are produced by Coleophoma empetri No. 11899, A. nidulans, A. aculeatus, A. sydowi and Glarea lozoyensis, respectively.…”

Section: Introductionmentioning

confidence: 84%

FR220897 and FR220899, Novel Antifungal Lipopeptides from Coleophoma empetri No. 14573

Kanasaki¹,

Abe²,

Kobayashi³

et al. 2006

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Novel antifungal lipopeptides, FR220897 and FR220899, were isolated from the fermentation broth of a fungal strain No. 14573. This strain was identified as Coleophoma empetri No. 14573 from morphological and physiological characteristics. FR220897 and FR220899 showed antifungal activities against Aspergillus fumigatus and Candida albicans attributed to inhibition of 1,3-bglucan synthesis. Furthermore, FR220897 was effective in a murine model of systemic candidiasis.

“…These compounds belong to the echinocandin family, a class of antifungal agents that act on the fungal cell wall by inhibiting glucan synthesis. The members of the echinocandin family of fungal origin are FR901379 [14,15], echinocandin B [16], aclueacins [17], mulundocandin [18] and pneumocandins [19], which are produced by C. empetri No. 11899, Aspergillus nidulans, A. aculeatus, A. sydowi and Glarea lozoyensis, respectively.…”

Section: Discussionmentioning

confidence: 99%

FR209602 and Related Compounds, Novel Antifungal Lipopeptides from Coleophoma crateriformis No. 738

Kanasaki¹,

Sakamoto²,

Hashimoto³

et al. 2006

Self Cite

Novel antifungal lipopeptides, FR209602, FR209603 and FR209604, were isolated from the fermentation broth of a fungal strain No. 738 which was identified as Coleophoma crateriformis from morphological and physiological characteristics. The antibiotics were purified by solvent extraction, HP-20, YMC-ODS and silica gel column chromatography and lyophilization. These compounds were structurally similar to FR901379 previously reported by ourselves which had a sulfate residue in the cyclic peptide portion.