Sclerotiamide:  A New Member of the Paraherquamide Class with Potent Antiinsectan Activity from the Sclerotia of <i>Aspergillus sclerotiorum</i>

Whyte, Authrine C.; Gloer, James B.; Wicklow, Donald T.; Dowd, Patrick F.

doi:10.1021/np960607m

Cited by 126 publications

(114 citation statements)

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“…Here, most of the isolates were also from the human respiratory tract. Aspergillus sclerotiorum is found worldwide, commonly isolated from soil, and reported as a species of biotechnological importance due to its ability to produce a wide range of compounds (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

et al. 2017

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A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the United States and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were the internal transcribed spacer (ITS) region, and fragments of the beta-tubulin (BenA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes. The drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A. pseudosclerotiorum (23.5%). Other species identified were A. sclerotiorum (17.6%), A. ochraceus (8.8%), A. subramanianii (8.8%), and A. insulicola and A. ochraceopetaliformis, with two isolates (5.9%) of each. The drugs that showed the most potent activity were caspofungin, micafungin, and terbinafine, while amphotericin B showed the least activity.KEYWORDS Aspergillus, Circumdati section, clinical isolates, molecular identification, phenotypic identification S ection Circumdati includes aspergilli with biseriate conidial heads in shades of yellow to ochre, with mostly globose vesicles, and sclerotia variable in shape and color (1-3). It contains 26 species (3), with A. ochraceus being the best known and described as an important producer of many extrolites, including the mycotoxin ochratoxin A (3-5). This metabolite has nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties (6, 7) and is commonly found in coffee, rice, beverages, and other contaminated foodstuffs (3,8). Several species in this section have been involved in different types of infections, such as onychomycosis, caused by A. insulicola, A. melleus, A. ochraceopetaliformis, A. persii, A. sclerotiorum, and A. westerdijkiae (9-14); otomycosis, caused by A. sclerotiorum (15); skin infection, caused by A. westerdijkiae (12); and pulmonary aspergillosis and osteomyelitis, caused by A. ochraceus (16,17). Moreover, A. ochraceus, A. sclerotiorum, and A. westerdijkiae have been repetitively isolated from clinical specimens of immunocompromised patients, although in such cases their pathogenic role is uncertain (18)(19)(20)(21)(22).There are few data on the in vitro antifungal susceptibility of species within section Circumdati. The azoles, especially itraconazole, appear to have good activity against A.

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Section: Discussionmentioning

confidence: 99%

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

et al. 2017

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“…This report, and a recent paper by Whyte and Gloer, 84) describing the isolation of sclerotamide from Aspergillus sclerotiorum constitute the first examples of paraherquamide derivatives isolated outside of the Penicillia.…”

Section: The Paraherquamides Marcfortines and Related Alkaloidsmentioning

confidence: 70%

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Williams

2002

Chem. Pharm. Bull.

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The paraherquamides constitute an unusual family of prenylated indole alkaloids that are secondary metabolites produced by Penicillium sp. and Aspergillus sp. fungi. This review will cover both the biosynthesis as well as the chemical synthesis of this family of natural products. Particular emphasis will be placed on the provocative hypothesis that the core bicyclo[2.2.2]diazaoctan ring system, which is common to this entire family, is formed by a biological DielsAlder reaction.Despite its widespread use in synthetic organic chemistry, the Diels-Alder cycloaddition reaction does not occur frequently in nature. 1,2) There are just a few reports in the literature claiming the identification of an enzyme that catalyzes this most ubiquitous synthetic ring-forming reaction. [3][4][5][6] A possible explanation for this is that, enzymes generally catalyze reactions by stabilizing the structure and charge of the developing transition state. For most reactions subject to this stratagem of catalysis, both the starting substrate and the product differ significantly with respect to structure from the transition state; it is this fundamental difference that allows for turnover; i.e., both the product and the starting substrate must bind to the enzyme less tightly than the transition state structure. In the Diels-Alder reaction, the transition state is highly ordered and closely resembles the structure of the product (see Fig. 1, below). In other words, an enzyme that was designed to stabilize the transition state structure for this reaction would be expected to be inhibited by the product (via tight binding) and turnover (thus catalysis) would be precluded. It is from within the excitement of this fundamental question, that this review will hold as a guiding light.The only examples of protein-catalyzed Diels-Alder reactions are those of catalytic antibodies that have recently been shown to catalyze the intermolecular [4ϩ2] cycloaddition reaction.7-9) In these cases, the initial Diels-Alder adducts were high-energy substances that significantly change their structure or conformation after the initial cyclocondensation and were subsequently released from the antibody CDR (allowing for turnover). In addition, ribozymes have been reported to catalyze the Diels-Alder reaction and findings in this area have been reviewed. 10) The Penicillium sp. that produces the brevianamides/paraherquamides may be a rare, but vitally important example of the existence of DielsAlderases. It is further significant to note in the context of the catalytic antibody stratagem that, the brevianamide DielsAlder adducts (which are proposed to be the brevianamides themselves) are very rigid substances; therefore, a significant change in conformation or structure is either impossible or highly unlikely. Elucidation of the mechanism for turnover in the purported paraherquamide and brevianamide [4ϩ2] cycloaddition reaction should be an extremely interesting and significant finding.In order to do proper justice to the history of the biosynthetic Diels-Alder p...

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“…3). Previous studies have revealed that the 2-oxindole alkaloid type compounds adopted a conformation in which the central five-membered ring is orthogonal to the plane of the oxindole subunit [9]. NOESY correlations between H-4 and H-10a, H-25 and between 19-NH and H-10a indicated that they were both on the face of the cyclopentanoid ring that orients them toward H-4, fixing the relative stereochemistry at C-3 as shown.…”

Section: Resultsmentioning

confidence: 89%

“…Indole alkaloids possessing an unusual bicyclo [2.2.2] diazaoctane ring system have been isolated from different genera of fungi such as Aspergillus [12,9,13], Penicillium [14ϳ16] and Malbranchea [17]. 1 was a new member of this group of compounds, it possessed a skeleton expected to be an intermediate in the biosynthesis of the citrinadins A and B reported as a novel class of pentacyclic spiroindolinone alkaloids in 2005 [18].…”

Section: Resultsmentioning

confidence: 99%

Chrysogenamide A from an Endophytic Fungus Associated with Cistanche deserticola and Its Neuroprotective Effect on SH-SY5Y Cells

et al. 2008

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Chrysogenamide A (1), a new member of the macfortine group of alkaloids, along with four known compounds (2ϳ5) were identified from Penicillium chrysogenum No. 005, an endophytic fungus associated with Cistanche deserticola Y. C. Ma. The new structure was elucidated on the basis of comprehensive spectral analysis. 1 exhibited a neurocyte protection effect against oxidative stress-induced cell death in SH-SY5Y cells.

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Sclerotiamide: A New Member of the Paraherquamide Class with Potent Antiinsectan Activity from the Sclerotia of Aspergillus sclerotiorum

Cited by 126 publications

References 12 publications

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Chrysogenamide A from an Endophytic Fungus Associated with Cistanche deserticola and Its Neuroprotective Effect on SH-SY5Y Cells

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Sclerotiamide: A New Member of the Paraherquamide Class with Potent Antiinsectan Activity from the Sclerotia of Aspergillus sclerotiorum

Cited by 126 publications

References 12 publications

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels&ndash;Alder Construction

Chrysogenamide A from an Endophytic Fungus Associated with Cistanche deserticola and Its Neuroprotective Effect on SH-SY5Y Cells

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Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction