Design, synthesis, and biological evaluation of novel berberine derivatives against phytopathogenic fungi

Abstract

BACKGROUND: The abuse of chemical fungicides not only leads to toxic residues and resistance in plant pathogenic fungi, but also causes environmental pollution and side effects on in humans and animals. Based on the antifungal activities of berberine, seven different types of berberine derivatives (A1-G1) were synthesized, and their antifungal activities against six plant pathogenic fungi were evaluated (Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Phytophthora capsici, Sclerotinia sclerotiorum, and Magnaporthe oryzae). RESULTS:The results for antifungal activities in vitro showed that berberine derivative E1 displayed good antifungal activity against R. solani with a median effective concentration (EC 50 ) of 1.77 ∼g ml −1 , and berberine derivatives F1 and G1 demonstrated broad-spectrum antifungal activities with EC 50 values ranging from 4.43 to 42.23 ∼g ml −1 against six plant pathogenic fungi. Berberine derivatives (E2-E29, F2-F18, and G2-G9) were further synthesized to investigate the structure-activity relationship (SAR), and compound E20 displayed significant antifungal activity against R. solani with an EC 50 value of 0.065 ∼g ml −1 . Preliminary mechanism studies showed that E20 could cause mycelial shrinkage, cell membrane damage, mitochondrial abnormalities and the accumulation of harmful reactive oxygen species, resulting in cell death in R. solani. Moreover, in vivo experimental results showed that the protective effect of E20 was 97.31% at 5 ∼g ml −1 , which was better than that of the positive control thifluzamide (50.13% at 5 ∼g ml −1 ).CONCLUSION: Berberine derivative E20 merits further development as a new drug candidate with selective and excellent antifungal activity against R. solani.

Discovery of Aryloxy-, Arylthio-, and Arylamino-Containing Acethydrazides as Fungicidal Agents

“…However, with the long-term use of traditional fungicides, the resistance of plant pathogens such as Botrytis cinerea and Colletotrichum gloeosporioides in facility vegetables has become more serious. Therefore, the development of novel fungicides with unique targets is imminent. − At present, there are more than 230 commercial fungicides reported by FRAC, and their application has provided an important guarantee for the sustainable development of global agriculture.…”

Inhibitory Activity Against Rhizoctonia Solani and Chemical Composition of Extract from Moutan Cortex

“…Therefore, we need to have a deeper understanding of this issue. [7][8]39] Bio-derived metabolites could serve as an ideal alternative to chemical synthetic fungicides for controlling and reducing RSB. Among these, plant extracts and secondary metabolites could be suitable substances for discovering and creating antifungal activities.…”

“…[5][6] However, problems such as environmental contamination, compromised food safety, and damage to non-target organisms have arisen from the prolonged and careless use of chemically synthesized fungicides. [7][8][9] Therefore, low-toxicity fungicides derived from plants have emerged as suitable alternatives and are gaining significant attention from researchers. [10][11][12][13][14] Moutan cortex (MC), derived from the root bark of Paeonia suffruticosa Andrews, has been utilized in China's clinical practice for nearly 2000 years.…”

Discovery of tryptanthrin analogues bearing F and piperazine moieties as novel phytopathogenic antibacterial and antiviral agents

“…[30][31][32] 2.4 Mode of action experiment SEM observation, ROS, apoptosis, biofilm, and the Xoo cells growth curve assay were conducted following previously published methods. [33][34][35][36][37]…”