Synthesis, bioactivity and functional evaluation of linker-modified allatostatin analogs as potential insect growth regulators

Insect growth regulators play an important role in integrated pest management strategies. The FGLa–allatostatins (ASTs) are a family of neuropeptides that can inhibit juvenile hormone (JH) biosynthesis by the corpora allata (CA) of Diploptera punctata in vitro, are regarded as insect growth regulator candidates. In the search for new potential mimics and to explore the effect of linker length on inhibiting JH biosynthesis, a series of AST analogs were synthesized by modifying the linker of K24, which was found to have a significant effect on JH biosynthesis in vitro in our previous study. Functional evaluation demonstrated that all the target compounds can activate the Dippu-AstR, albeit with different potencies. Analog L6 with the longest linker (n = 5), exhibited not only a promising effect on inhibition of JH biosynthesis both in vitro and in vivo, but also good activity in inhibiting basal oocyte growth. Structure–activity relationships (SAR) studies showed that longer linkers provided greater contribution to activity.

A series of AST analogs were synthesized by modifying the linker of K24. The bioassay results showed that all target analogs exhibited different potencies in inhibiting JH biosynthesis and activating Dippu-AstR as a consequence of vary linker length. Analog L6, with the longest linker (n = 5), had outstanding effect on inhibiting JH biosynthesis in vitro and in vivo, as well as good activity in inhibiting basal oocyte growth.Figure optionsDownload as PowerPoint slide