Antimalarials and Phytotoxins from Botryosphaeria dothidea Identified from a Seed of Diseased Torreya taxifolia

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 target metabolic pathways of the plastid; thus, they may also 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 isomeric phytotoxins, FRT-A and flavipucine (or their enantiomers, sapinopyridione and (-)-flavipucine), and two new unstable γ-lactam alkaloids dothilactaenes A and B. The isomeric mixture of phytotoxins displayed strong phytotoxicity against both a dicot and a monocot and moderate cytotoxicity against a panel of cell lines. Dothilactaene A showed no activity. Dothilactaene B was isolated from the active fraction, which showed moderate in vitro antiplasmodial activity with high selectivity index. In spite of this activity, its instability and various other biological activities shown by related compounds would preclude it from being a viable antimalarial lead.

Phytochemical, Antiplasmodial, Cytotoxic and Antimicrobial Evaluation of a Southeast Brazilian Brown Propolis Produced by Apis mellifera Bees

“…The in vitro antiplasmodial activity was determined against two Plasmodium falciparum strains namely, D6 (chloroquine‐sensitive) and W2 (chloroquine‐resistant). The activity was measured by a colorimetric assay that determines the parasitic lactate dehydrogenase (pLDH) activity, as described earlier [58] . Briefly, red blood cells (200 μL) infected with P. falciparum in RPMI 1640 medium supplemented with 10 % human serum and 60 μg/mL amikacin with 2 % parasitemia and 2 % hematocrit, were added to the wells of a 96‐well plate containing serially diluted samples (10 μL) and incubated for 72 h in an incubator that maintains a temperature of 37 °C and an environment of 90 % N 2 , 5 % O 2 , and 5 % CO 2 .…”

Phytotoxic Secondary Metabolites from Fungi

“…It was toxic to three cypress species (Cupressus arizonica, C. macrocarpa, and C. sempervrens) by cutting twig assay [297]. The 3:1 mixture of FRT-A (461) and FRT-B (462) showed strong phytotoxic activity to plants bentgrass (Agrostis stolonifera) and lettuce (Lactuca sativa) by seedling growth assay [298].…”

Identification of Mellein as a Pathogenic Substance of Botryosphaeria dothidea by UPLC-MS/MS Analysis and Phytotoxic Bioassay

“…However, previous studies on the metabolites of B. dothidea only involved their anticancer, antibacterial, antioxidant, and cytotoxic activities. − It still remains unclear whether B. dothidea produces pathogenic substances related to the occurrence of apple ring rot and what they are.…”