Regioselective Claisen-Schmidt Adduct of 2-undecanone from Houttuynia cordata Thunb as insecticides against Solenopsis invicta and repositioning plant fungicides against Colletotrichum fragariae

Authors: KURMANBAYEVA, AIGERIM - University Of Mississippi; OSPANOV, MEIRAMBEK - University Of Mississippi; Tamang, Prabin; SHAH, FARHAN MAHMOOD - University Of Mississippi; ALI, ABBAS - University Of Mississippi; Cantrell, Charles; DINARA, SATMBEKOVA - Asfendiyarov Kazakh National Medical University; DATKHAYEV, UBAIDILLA - Asfendiyarov Kazakh National Medical University; KHAN, IKHLAS - University Of Mississippi; IBRAHIM, MOHAMED - University Of Mississippi

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2023
Publication Date: 8/17/2023
Citation: Kurmanbayeva, A., Ospanov, M., Tamang, P., Shah, F., Ali, A., Cantrell, C.L., Dinara, S., Datkhayev, U., Khan, I.A., Ibrahim, M.A. 2023. Regioselective Claisen-Schmidt Adduct of 2-undecanone from Houttuynia cordata Thunb as insecticides against Solenopsis invicta and repositioning plant fungicides against Colletotrichum fragariae. Molecules. https://doi.org/10.3390/molecules28166100.
DOI: https://doi.org/10.3390/molecules28166100

Interpretive Summary: The U.S. Department of Agriculture (USDA) has established research programs to fight the phytopathogen Colletotrichum fragariae and the invasive red imported fire ant, Solenopsis invicta. C. fragariae is well known to cause anthracnose disease in several fruits and vegetables while S. invicta is known for its aggressive behavior and painful stings and being the cause of significant damage to crops, as well as harm to humans and animals. Many plants have been studied for their potential activity against C. fragariae and S. invicta. Among the studied plants, Houttuynia cordata Thunb, has been shown to contain 2-undecanone which is known for its antifungal activity and mosquito repelling activity. In this study, we have synthesized analogs of 2-undecanone and evaluated these analogs for antifungal activity and activity against the red imported fire ant. Two of the analogs evaluated exhibited activity superior to 2-undecanone.

Technical Abstract: The U.S. Department of Agriculture (USDA) has established research programs to fight the phytopathogen Colletotrichum fragariae and the invasive red imported fire ant, Solenopsis invicta. C. fragariae is well known to cause anthracnose disease in several fruits and vegetables while S. invicta is known for its aggressive behavior and painful stings and being the cause of significant damage to crops, as well as harm to humans and animals. Many plants have been studied for their potential activity against C. fragariae and S. invicta. Among the studied plants, Houttuynia cordata Thunb, has been shown to contain 2-undecanone which is known for its antifungal activity against Colletotrichum gloesporioides. 2-undecanone and DEET (N, N-diethyl-meta-toluamide) showed significant repellency at 62.5 µg/g against S. invicta based of the mean amount of sand removed with LC50 of 44.59 µg/g against S. invicta workers. However, neither H. cordata extract nor 2-undecanone had shown activity against C. fragariae despite its known activity against C. gloesporioides, which in turn motivates us for repositioning 2-undecanone as a selected candidate for Claisen-Schmidt condensation that enable access to several analogs (2a-f). Among the prepared analogs, (E)-1-(3-methylbenzo[b]thiophen-2-yl)dodec-1-en-3-one (2b) and (E)-1-(5-bromothiophen-2-yl)dodec-1-en-3-one (2f) showed promising activity against C. fragariae revealing distinctive structural activity relationship (SAR). The structures of the generated leads were established based of 1D- and 2D NMR analysis. As expected, the leads revealed a clear regioselectivity pattern through forming the C=C alkene bond at position C-1. Our data opens the window for further lead optimization and product development in the context of managing C. fragariae and S. invicta.