### Quantitative Structure-Activity Relationship Studies and Molecular Modelling of Octopaminergic 2-(Substituted benzylamino)-2-thiazolines and Oxazolines against Nervous System of Periplaneta americana L.

> Canping Pan,a Akinori Hirashima ,a* Jun Tomita,a Eiichi Kuwano,a Eiji Taniguchia and Morifusa Eto b
> a Department of Agricultural Chemistry, Kyushu University 46-02, Fukuoka 812-81, Japan
> b Present address: Miyakonojo National College of Technology, 473-1 Yoshio-cho, Miyakonojo 885, Japan

*To whom correspondence should be addressed. Fax:+81-092-642-2864; E-mail: ahirasim@agr.kyushu-u.ac.jp

Received June 4, 1997
Accepted June 13, 1997
Published June 17, 1997

#### Copyright © 1997 Internet Journal of Science - Biological Chemistry

#### Abstract

The quantitative structure-activity relationship (QSAR) of octopaminergic 2-(substituted benzylamino)-2-thiazolines (SBTs) and 2-(substituted benzylamino)-2-oxazolines (SBOs) against the thoracic nerve cord of American cockroach, Periplaneta americana L., was examined using reported physicochemical parameters and multiple linear regression analysis. The electronic nature of a substituent was the most important followed by the steric hydrophobic effect for SBT in terms of Vmax: with the more electron-donating and the less bulky the substituent at m-position, the greater the activity. The electronic nature of a substituent of SBO was considered to be the most important descriptor, followed by the steric and hydrophobic effects in terms of Vmax: the more hydrophobic and the more electron-withdrawing the substituent, the greater the activity. SBO with a 3-chlorophenyl group (29) was more active than its thiazoline derivative, 2-(3-chlorophenylamino)-2-thiazoline (CIT) in terms of Ka and Vmax: Ka and Vmax of 29 were 0.52 M and 40% relative to OA, whereas those of CIT were 1.61 M and 23% relative to OA, respectively. Computer-Assisted Molecular Fitting (CAMF) was accomplished using the empirical SEAL fitting which takes into account steric and electrostatic parameters for structure alignments. Both the electrostatic properties of these compounds evaluated by the wavefunction data that recalled from MOPAC(PM3) and superimposition of energy-minimized OA and 29 revealed electronic and conformational similarities that might account for the high activity of 29. The current study indicates that SBTs and SBOs with certain substituents can be potent agonists to OA receptors associated with the activation of adenylate cyclase. And it provides new information regarding the efficiency and potency of oxazoline and thiazoline derivatives. QSAR and preliminary modelling studies demonstrate that the enhanced potency of SBOs and SBTs may be due to the potential electronic interaction between the m-substituted benzyl ring and the undefined receptor site.

Key Words: QSAR, Octopaminergic agonists, Molecular modelling, Oxazolines, Thiazolines, Periplaneta americana

#### Table of Contents:

> 1. Introduction

> 2. Methods

> > 2.1 Bioassay
> > 2.2 Computational Methodology

> 3. Results and Discussion

> > 3.1. QSAR of SBT

> > 3.2. QSAR of SBO

> > 3.3. Molecular Modelling

> > > 3.3.1. Part 1

> > > 3.3.2. Part 2

> > > 3.3.3. Part 3

> 4. Conclusions

> 5. Acknowledgments

> 6. References

Copyright © 1997 Internet Journal of Science - Biological Chemistry