3D-QSAR based optimization of insect neuropeptide allatostatin analogs

Bioorg Med Chem Lett. 2019 Apr 1;29(7):890-895. doi: 10.1016/j.bmcl.2019.02.001. Epub 2019 Feb 2.

Abstract

Allatostatins (AST) are neuropeptides originally described as inhibitors of juvenile hormone (JH) synthesis in insects. Consequently, they have been considered as potential lead compounds for the discovery of new insect growth regulators (IGRs). In the present work, receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) was studied with 48 AST analogs, and a general approach for novel potent bioactive AST analogs is proposed. Hence, six novel AST analogs were designed and synthesized. Bioassays indicated that the majority novel analogs exhibited potent JH inhibitory activity, especially analog A6 (IC50: 3.79 nmol/L), which can be used as lead compound to develop new IGRs.

Keywords: 3D-QSAR; Allatostatins analogs; IGRs; Neuropeptides; Optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cockroaches / chemistry
  • Insect Proteins / chemical synthesis
  • Insect Proteins / chemistry*
  • Insect Proteins / metabolism
  • Juvenile Hormones / antagonists & inhibitors
  • Juvenile Hormones / chemistry*
  • Juvenile Hormones / metabolism
  • Molecular Docking Simulation
  • Molecular Structure
  • Neuropeptides / chemical synthesis
  • Neuropeptides / chemistry*
  • Neuropeptides / metabolism
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Receptors, Neuropeptide / chemistry
  • Receptors, Neuropeptide / metabolism

Substances

  • Insect Proteins
  • Juvenile Hormones
  • Neuropeptides
  • Receptors, Neuropeptide
  • allatostatin