In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors.

Lijun Yang,Dawei Wang,Jing Wang,Dejun Ma,Zhen Xi,Di Zhang,Nuo Zhou,Han Xu

doi:10.3390/molecules26226979

Lijun Yang, Dawei Wang + Show 6 more

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https://doi.org/10.3390/molecules26226979

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Abstract

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.

Highlights

IntroductionThere are many ways to control weeds in crop fields, and using herbicides is the most effective and economical approach to decimate weeds [5]
The results indicated that compound 1 was located at the catalytic site of Synechococcus Phytoene desaturase (PDS) (Figure 2), which was similar to that of the norflurazon–OsPDS system [14]
We found that 2a and 3h could bind to the recombinant Synechococcus PDS protein which was immobilized on the sensor chip, and the KD values for

Summary

Introduction

There are many ways to control weeds in crop fields, and using herbicides is the most effective and economical approach to decimate weeds [5]. The discovery of new herbicides is essential to crop protection [6,7,8]. Phytoene desaturase (PDS) is an important target for the discovery of herbicides [9]. It is a rate-limiting enzyme involved in the biosynthesis of carotenoids, which catalyzes the symmetric desaturation of phytoene to carotene. Inhibition of PDS within plants could block the biosynthesis of carotene and lead to the accumulation of phytoene, which, in turn, would result in the photooxidation of the plant cell. The treated plants would develop a unique whitening symptom on the new leaves, followed by the full whitening effect of the entire leaves, and death [10,11]

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Conclusion