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Malformin A1, a cyclic pentapeptide, was isolated from the marine-derived fungus Aspergillus tubingensis IFM 63452. The identity of the compound was established based on TOFMS and H NMR data. Malformin A1 exhibited trypanocidal activity against Trypanosoma congolense (IC50: 15.08 ng/mL). Interestingly, the compound was selective for T. congolense rendering a selectivity index value that ranged from 3.33 to 4.67. It also demonstrated cytotoxicity against HeLa (IC50: 50.15 ng/mL) and P388 (IC50: 70.38 ng/mL) cell lines. To further identify the possible mechanism of its cytotoxic effect, immunofluorescence staining was conducted to follow the epigenetic changes induced by the compound in the amino acid lysine of histone H3 and H4 in HeLa. The compound induced repressive levels of H3K27me3, H3K27ac and H4K5ac, and enhanced levels of H3K9me2, H3K9me3 and H4K16ac supporting the compound’s chemotherapeutic potential.

mycosphere

Trypanocidal activity, cytotoxicity and histone modifications induced by malformin A1 isolated from the marine-derived fungus Aspergillus tubingensis IFM 63452