--> Inetrnet Journal of Science: Canping Pan, Akinori Hirashima et al., Conclusions etc.


In summary, the above studies demonstrate that SBTs and SBOs with certain substituents can be potent agonists to OA receptors associated with the activation of adenylate cyclase. And they provide new information regarding the efficiency and potency of oxazoline and thiazoline derivatives. QSAR and preliminary modelling studies suggest that the enhanced potency of SBOs and SBTs may be due to the potential electronic interaction of the m-substituted benzyl ring with the undefined pocket or residue at the receptor site. The steric demands are also important especially of SBTs and essential for the molecular recognition at the OA receptor site as shown by both the QSAR and the molecular fitting models by the SEAL technology. These important information may help to point the way towards developing extremely potent and relatively specific OA agonists which could be useful as insectistatics rather than insecticidal agents with reduced toxicity for vertebrates.

An important messsage from this study for those involved in the design of bioactive molecules is that quantum chemistry and molecualr modelling techniques might provide mechanistic insight where structure variation is far beyond the reach of the classic QSAR methods. In the meantime, the fact that conformational flexibility and further similarity indics in this study for SBTs and SBOs seem to deal well with the QSAR results suggests more fruitful directions for analogue synthesis. And we believe that such established computing systems as CAChe™ or other packages may be offering interesting resourses of molecular orbitals and other indices like similarity indice etc. to favour the structure-activity relationship study, as it's reasonable and reliable to translate chemical constitutions into numerical values via topological methodologies. Such studies will hopefully improve the understanding of octopaminergic agonist-receptor interaction mechanisms, and may lead to the discovery of new insectistatical agents which have improved potency and effectiveness.


We thank Emeritus Prof. Toshio Fujita of Kyoto University and Tanabe Pharmacology Co. Japan for donating the QSAR program. And we are grateful to Prof. Takaaki Sonoda of Institute of Advanced Material Study, Kyushu University, Japan for allowing us to use the CAChe Groupserver IBM RS6000. We also want to thank MicroSimulations Co. for providing evaluation project for Powerit1.0 and related MicroSimulation software. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.


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