A potential insect growth regulator for cockroach control: design, synthesis and bioactivity of N-terminal-modified allatostatin analogues.

BACKGROUND: The FGLa-allatostatins (ASTs) are a family of neuropeptides that can inhibit juvenile hormone biosynthesis by the corpora allata (CA) in vitro, and therefore they are regarded as insect growth regulator (IGR) candidates for pest control. In our previous studies, an AST mimic, H17, was found to have a significant effect on JH biosynthesis by cockroach CA, both in vitro and in vivo. To discover new potential mimics and explore the substituent effect on the inhibition of JH biosynthesis, 30 analogues, modified with various substituents on the benzene ring at the N-terminus of lead compound H17, were designed and synthesised. Their bioactivity in inhibiting JH biosynthesis by the CA of Diploptera punctata and the potency of M9, M10 and M11 in activation of Dippu-AstR were evaluated.

RESULTS: All the analogues showed an effect on JH biosynthesis by CA in vitro. M9, M10 and M11 can activate the Dippu-AstR, albeit with much lower potency than that of AST 1. M11 also exhibited improved in vitro activity (IC50 6.98 nm) in comparison with the lead compound H17 (IC50 29.5 nm). In particular, M11 displayed good in vivo activity in inhibiting JH biosynthesis and basal oocyte growth.

CONCLUSION: The structure-activity relationship studies suggest that different positions of substituents on the benzene ring of the cinnamic acid can lead to different activities. The para-substitution on the benzene ring plays an important role in inhibiting JH biosynthesis in vitro. Moreover, M11 is considered to be a potential IGR for cockroach control. © 2016 Society of Chemical Industry.