title: Synthesis, biological activity, and hologram quantitative structure-activity relationships of novel allatostatin analogues.
abstract: Cockroach-type allatostatins (FGLamides) (ASTs) can inhibit the production of juvenile hormone in vitro, and they therefore are regarded as possible insect growth regulator (IGR) candidates for pest control. However, several shortcomings, such as the absence of in vivo effects, rapid degradation, and high production costs, preclude their practical use in pest management. To discover new IGRs, 25 novel analogues of pentapeptide (Y/FXFGLa) were designed and synthesized with different aromatic acids, fatty acids, and dicarboxylic acids as the Y/FX region replacements on the basis of previous results. Their bioactivities in vitro were determined, and the results showed that eight analogues (K14, K15, K17, K18, K19, K23, K24, and K25) were more active than the lead, core region pentapeptide. The IC(50) values of K15 and K24 (IC(50) = 1.79 and 5.32 nM, respectively) were even lower than that of the natural AST, Dippu-AST 1(IC(50) = 8 nM), which indicated both analogues have better activity than Dippu-AST 1; particularly, K15 has better activity than most natural Dippu-ASTs. A predictable and statistically meaningful hologram quantitative structure-activity relationship (HQSAR) model of 32 AST analogues (28 as training sets and 4 as test sets) was obtained. The final model suggested that a potent AST analogue should contain an aromatic group, a linker of appropriate length, and the FGLa portion. These results will be useful in the design of new AST analogues that are structurally related to the training set compounds.
authors: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China.
authors: Zhen-Peng
authors: ZP
authors: Kai
authors: Juan
authors: J
authors: Huang
authors: Yong
authors: Y
authors: Xie
authors: Stephen S
authors: SS
authors: Tobe
authors: Yun
authors: Y
authors: Ling
authors: Li
authors: L
authors: Zhang
authors: Yi-Chen
authors: YC
authors: Zhao
authors: Xin-Ling
authors: XL
authors: Yang
mesh_terms: D000818:Animals; D003058:Cockroaches; D005260:Female; D006727:Hormone Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D006727:Hormone Antagonists; D009479:Neuropeptides; C076523:allatostatin