Discovery of metyltetraprole: Identification of tetrazolinone pharmacophore to overcome QoI resistance

  • Bioorg Med Chem. 2020 Jan 1;28(1):115211. doi: 10.1016/j.bmc.2019.115211.
Yuichi Matsuzaki  1 ,  Yuya Yoshimoto  2 ,  Sadayuki Arimori  2 ,  So Kiguchi  2 ,  Toshiyuki Harada  2 ,  Fukumatsu Iwahashi  2
Affiliations
  • 1. Health and Crop Sciences Research Laboratory, Sumitomo Chemical Co., Ltd., Takarazuka, Japan. Electronic address: [email protected].
  • 2. Health and Crop Sciences Research Laboratory, Sumitomo Chemical Co., Ltd., Takarazuka, Japan.
PMID: 31753801 DOI: 10.1016/j.bmc.2019.115211
Abstract

Quinone outside inhibitors (QoIs) are one of the major agricultural fungicide groups used worldwide. However, the development of resistance by different pathogenic species associated with specific mutation at the target gene site is becoming a critical issue for the sustainable use of QoIs. The authors aimed to design a novel QoI molecule to overcome the aforementioned issue. A rational approach to avoid steric hindrance between the QoI molecule and the mutated target site was successfully employed. The resulting compound, metyltetraprole, is characterized by 3-substituted central ring with a tetrazolinone moiety, the key structure to retain potent activity against QoI-resistant mutants. Metyltetraprole is a promising new fungicide under commercial development, and its development in this study has paved the way to overcoming resistance to QoI fungicides.

Keywords
Fungicide resistance; G143A; Metyltetraprole; QoI.
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