Antibacterial spirooxindole alkaloids from Penicillium brefeldianum inhibit dimorphism of pathogenic smut fungi

Huajun Shi; Jinyan Jiang; Hang Zhang; Haimei Jiang; Zijie Su; Dandan Liu; Ligang Jie; Fei He

doi:10.3389/fmicb.2022.1046099

Antibacterial spirooxindole alkaloids from Penicillium brefeldianum inhibit dimorphism of pathogenic smut fungi

Front Microbiol. 2022 Nov 14:13:1046099. doi: 10.3389/fmicb.2022.1046099. eCollection 2022.

Authors

Huajun Shi¹, Jinyan Jiang^{1

2}, Hang Zhang¹, Haimei Jiang¹, Zijie Su¹, Dandan Liu³, Ligang Jie^{1

3}, Fei He^{1

3}

Affiliations

¹ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
² Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
³ Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Abstract

Three new antibacterial spirooxindole alkaloids, spirobrefeldins A-C (1-3), together with four known analogs, spirotryprostatin M (4), spirotryprostatin G (5), 12β-hydroxyverruculogen TR-2 (6), and 12α-hydroxyverruculogen TR-2 (7), were isolated from terrestrial fungus Penicillium brefeldianum. All the new compounds were elucidated extensively by the interpretation of their NMR (1D and 2D) spectra and high-resolution mass data, and their absolute configurations were determined by computational chemistry and CD spectra. The absolute configurations of spiro carbon C-2 in spirotryprostatin G (5) and spirotryprostatin C in literature were reported as S, which were revised to R based on experimental and calculated CD spectra. All the compounds were evaluated for their antimicrobial activities toward Pseudomonas aeruginosa PAO1, Dickeya zeae EC1, Staphylococcus epidermidis, Escherichia coli, and Sporisorium scitamineum. Compound 7 displayed moderate inhibitory activity toward dimorphic switch of pathogenic smut fungi Sporisorium scitamineum at 25 μM. Compounds 3 and 6 showed weak antibacterial activities against phytopathogenic bacterial Dickeya zeae EC1 at 100 μM.

Keywords: Penicillium brefeldianum; absolute configuration; antibacterial activities; fungal secondary metabolites; spirooxindole diketone piperazine.