Synthesis, Herbicidal Activity, and Structure-Activity Relationships of O-Alkyl Analogues of Khellin and Visnagin

Authors: Cantrell, Charles; TRAVAINI, MARIA LUCIA - Investigaciones Biológicas En Agroquímicos Rosario (INBIOAR SA); Bajsa-Hirschel, Joanna; SVENDSEN, LARA - Investigaciones Biológicas En Agroquímicos Rosario (INBIOAR SA); Reichley, Amber; SOSA, GUSTAVO - Investigaciones Biológicas En Agroquímicos Rosario (INBIOAR SA); Kim, Seong; Tamang, Prabin; Meepagala, Kumudini; DUKE, STEPHEN - University Of Mississippi

Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2023
Publication Date: 9/23/2023
Citation: Cantrell, C.L., Travaini, M., Bajsa Hirschel, J.N., Svendsen, L.D., Reichley, A.C., Sosa, G.M., Kim, S., Tamang, P., Meepagala, K.M., Duke, S.O. 2023. Synthesis, Herbicidal Activity, and Structure-Activity Relationships of O-Alkyl Analogues of Khellin and Visnagin. Journal of Agriculture and Food Chemistry. 71:14593-14603. https://doi.org/10.1021/acs.jafc.3c03254.
DOI: https://doi.org/10.1021/acs.jafc.3c03254

Interpretive Summary: Khellin and visnagin are furanochromones from the plant Ammi visnaga with a long history of use in a variety of medicinal applications. Some of the earliest medicinal reports on khellin and its preparations appeared in the literature in the early 1900’s. Khellin and visnagin were recently reported as potential new bioherbicides with phytotoxic activities comparable to some commercially available herbicides. In this study, we examined the effect synthetic modification of both khellin and visnagin on its phytotoxicity and antifungal activity. The primary goal was to produce more effective pesticides than the natural compounds khellin and visnagin and to allow for a better understanding of the importance that this functional group imparts relative to its desired biological activity. At least one analog was produced with increased phytotoxic activity relative to the parent molecule visnagin.

Technical Abstract: Khellin and visnagin furanochromones were recently reported as potential new bioherbicides with phytotoxic activities comparable to some commercially available herbicides. In this study, we examined the effect of o-alkylation and o-arylalkylation of both khellin and visnagin on its effect on phytotoxicity and antifungal activity. Synthetic analogs included O-demethyl khellin and visnagin, acetylated O-demethyl khellin and visnagin, O-benzylated demethyl khellin and visnagin, four O-demethyl alkylated khellin analogs, and six O-demethyl alkylated visnagin analogs many of which are reported here for the first time. Both acetate analogs of khellin and visnagin indicated were more active as phytotoxins on Lemna pausicostata than visnagin, with IC50 values of 71.7 micro M and 77.6 micro M, respectively. Complete loss of activity for all O-alkyl analogs with a carbon chain length of greater than 14 carbons was observed. The O-demethyl butylated visnagin analog was the most active compound found with an IC50 of 47.2 micro M against L. pausicostata. O-Demethyl ethylated analogs of both khellin and visnagin were as effective as khellin. In the antifungal bioautography bioassay against Colletotrichum. fragariae at 100 'g, the only active O-alkyl and O-arylalkyl analogs were O-ethylated, O-butylated, and O-benzylated visnagin analogs with zones of inhibition of 10, 9, and 9 mm, respectively, and comparable to visnagin and khellin.