Abstract
Two new cytochalasins, sclerotionigrin A (1) and B (2) were isolated together with the known proxiphomin (3) from the filamentous fungus Aspergillus sclerotioniger. The structures and relative stereochemistry of 1 and 2 were determined based on comparison with 3, and from extensive 1D and 2D NMR spectroscopic analysis, supported by high resolution mass spectrometry (HRMS). Compounds 2 and 3 displayed cytotoxic activity towards chronic lymphocytic leukemia cells in vitro, with 3 being the most active.
Highlights
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in the Western World
The formula was used for a query in Antibase2012 [34] with one resulting hit, proxiphomin (3)
The PK chain was closed via an ester bond assigned from HMBC correlations from the vinylic protons at δH 5.65 (H22) and 6.96 ppm (H21) to the carbonyl carbon at δC 163.5 ppm (C23) supported by the high chemical shift of the quaternary carbon at δC 85.4 ppm (C9) indicating that C9 is bound to oxygen, and a carbonyl group, similar to what is seen in several other cytochalasans [7]
Summary
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in the Western World. We have demonstrated that chaetoglobosin A, produced by Penicillium aquamarinum, selectively induces apoptosis in CLL cells with a median lethal concentration (LC50) value of 2.8 μM [10] Encouraged by this finding we searched for potential novel cytochalasan type of compounds in black aspergilli. In the sister clade Aspergillus subgenus Circumdati section Flavipedes, numerous cytochalasans have been reported [13,14,15,16,17,18,19,20,21,22,23,24,25,26] including aspochalasin A–D [27,28]. We have previously reported ochratoxin A, ochratoxin B and pyranonigrin A from this isolate [33]
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