In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity.

Celangulin V is a novel botanical insecticide with significant bioactivity and a unique molecular target, but its complex polyol ester structure hinders its broader application in agriculture. To discover new analogues of celangulin V with a simpler structure and enhanced biological activities, we initiated a research project aimed at simplifying its structure and assessing insecticidal efficacy. In this study, a series of novel 1-tetralone derivatives were designed via a structure-based rational design approach and synthesized by a facile method. The biological activities of the target compounds were determined against Mythimna separata (M. separata), Plutella xylostella, and Rhopalosiphum padi. The results revealed that most of the synthesized compounds exhibited superior activities compared to celangulin V. Remarkably, the insecticidal activity of compound 6.16 demonstrated 102-fold greater stomach toxicity than celangulin V against M. separata. In addition, certain compounds showed significant contact toxicity against M. separata, a finding not reported previously in the structural optimization studies of celangulin V. Molecular docking analysis illustrated that the binding pocket of compound 6.16 with the H subunit of V-ATPase was the same as celangulin V. This study presents novel insights into the structural optimization of botanical pesticides.

The haplotype-resolved genome of diploid Chrysanthemum indicum unveils new acacetin synthases genes and their evolutionary history.

Acacetin, a flavonoid compound, possesses a wide range of pharmacological effects, including antimicrobial, immune regulation, and anticancer effects. Some key steps in its biosynthetic pathway were largely unknown in flowering plants. Here, we present the first haplotype-resolved genome of Chrysanthemum indicum, whose dried flowers contain abundant flavonoids and have been utilized as traditional Chinese medicine. Various phylogenetic analyses revealed almost equal proportion of three tree topologies among three Chrysanthemum species (C. indicum, C. nankingense, and C. lavandulifolium), indicating that frequent gene flow among Chrysanthemum species or incomplete lineage sorting due to rapid speciation might contribute to conflict topologies. The expanded gene families in C. indicum were associated with oxidative functions. Through comprehensive candidate gene screening, we identified five flavonoid O-methyltransferase (FOMT) candidates, which were highly expressed in flowers and whose expressional levels were significantly correlated with the content of acacetin. Further experiments validated two FOMTs (CI02A009970 and CI03A006662) were capable of catalyzing the conversion of apigenin into acacetin, and these two genes are possibly responsible acacetin accumulation in disc florets and young leaves, respectively. Furthermore, combined analyses of ancestral chromosome reconstruction and phylogenetic trees revealed the distinct evolutionary fates of the two validated FOMT genes. Our study provides new insights into the biosynthetic pathway of flavonoid compounds in the Asteraceae family and offers a model for tracing the origin and evolutionary routes of single genes. These findings will facilitate in vitro biosynthetic production of flavonoid compounds through cellular and metabolic engineering and expedite molecular breeding of C. indicum cultivars.