Antimalarials and phytotoxins from Botryosphaeria dothidea identified from a seed of diseased Torreya taxifolia

Authors: KUMARIHAMY, MALLIKA - University Of Mississippi; ROSA, LUIZ - Universidade Federal De Minas Gerais; TECHEN, NATASCHA - University Of Mississippi; FERREIRA, DANEEL - University Of Mississippi; CROOM, EDWARD - University Of Mississippi; DUKE, STEPHEN - Retired ARS Employee; TEKWANI, BABU - University Of Mississippi; KHAN, SHABANA - University Of Mississippi; NANAYAKKARA, N.P. DHAMMIKA - University Of Mississippi

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/24/2020
Publication Date: 12/24/2020
Citation: Kumarihamy, M., Rosa, L.H., Techen, N., Ferreira, D., Croom, E.M., Duke, S.O., Tekwani, B.L., Khan, S., Nanayakkara, N. 2020. Antimalarials and phytotoxins from Botryosphaeria dothidea identified from a seed of diseased Torreya taxifolia. Molecules. https://doi.org/10.3390/molecules26010059.
DOI: https://doi.org/10.3390/molecules26010059

Interpretive Summary: The ethyl acetate extract from Botryosphaeria dothidea, an endophyte isolated from the seeds collected from Torreya taxifolia plant, showed antimalarial and phytotoxic activities in in vitro assays. Further separation of the extract using bioactivity-guided fractionation demonstrated a mixture of two known phytotoxins, fruit rot toxin A and flavipucine, and four new unstable '-lactam alkaloid dothilactaenes A, B, C, and D. Dothilactaenes B, C and D are diastereomers and showed strong antiplasmodial activity in vitro with high selectivity index. However, their instability and various undesirable biological activities shown by the related compounds make them impossible to be further developed as viable antimalarial drugs.

Technical Abstract: The metabolic pathways in the apicoplast organelle of Plasmodium parasites are similar to those in plastids in plant cells and are suitable targets for malaria drug discovery. Some phytotoxins released by plant pathogenic fungi have been known to inhibit metabolic pathways of the plastid; thus, they serve as potential antimalarial drug leads. An EtOAc extract of the broth of the endophyte Botryosphaeria dothidea isolated from a seed collected from a Torreya taxifolia plant with disease symptoms, showed in vitro antimalarial and phytotoxic activities. Bioactivity-guided fractionation of the extract afforded a mixture of two known phytotoxins, FRT-A and flavipucine (or their enantiomers, sapinopyridione and (-)-flavipucine), and four new unstable '-lactam alkaloids dothilactaenes A-D. Dothilactaenes B-D are diastereomers and showed strong in vitro antiplasmodial activity with high selectivity index. In spite of this activity, their instability and various undesirable biological activities shown by related compounds would preclude them from being viable antimalarial leads.