Chevalone C analogues and globoscinic acid derivatives from the fungus Neosartorya spinosa KKU-1NK1

Abstract

Four meroterpenoids, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11-dihydroxychevalone C, and 11-hydroxychevalone C and two ester epimers, 2S,4S-spinosate and 2S,4R-spinosate, together with seven known compounds, chevalones B, C, and E, tryptoquivaline, nortryptoquivaline, tryptoquivaline L, and quinadoline A were isolated from the fungus Neosartorya spinosa. Their structures were established based on spectroscopic data analyses. The theoretical ECD spectra of epimers, 2S,4S-spinosate and 2S,4R-spinosate were calculated to support the experimental results of their CD spectra. 1-hydroxychevalone C exhibited antimycobacterial activity against Mycobacterium tuberculosis with a MIC value of 26.4 μM. 1-Acetoxychevalone C and tryptoquivaline showed antimalarial activity against Plasmodium falciparum with IC₅₀ values of 6.67 and 2.65 μM, respectively. In addition, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11-dihydroxychevalone C and quinadoline A showed cytotoxicity against KB and NCI-H187 cancer cell lines with IC₅₀ values in the range of 32.7-103.3 μM.

Keywords: Antimalarial; Chevalones; Cytotoxicity; ECD calculations; Globoscinic acid derivatives; Meroterpenoids; Neosartorya spinosa.