Design, synthesis and evaluation of 3-arylidene azetidin-2-ones as potential antifungal agents against Alternaria solani Sorauer

Wang Delong; Wu Yongling; Wang Lanying; Feng Juntao; Zhang Xing

doi:10.1016/j.bmc.2017.11.003

Design, synthesis and evaluation of 3-arylidene azetidin-2-ones as potential antifungal agents against Alternaria solani Sorauer

Bioorg Med Chem. 2017 Dec 15;25(24):6661-6673. doi: 10.1016/j.bmc.2017.11.003. Epub 2017 Nov 4.

Authors

Wang Delong¹, Wu Yongling¹, Wang Lanying², Feng Juntao³, Zhang Xing¹

Affiliations

¹ Research & Development Center of Biorational Pesticide, Shaanxi Research Center of Biopesticide Engineering & Technology, Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Northwest A&F University, Yangling 712100, China.
² Research & Development Center of Biorational Pesticide, Shaanxi Research Center of Biopesticide Engineering & Technology, Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Northwest A&F University, Yangling 712100, China; College of Environment and Plant Protection, Hainan University, Haikou, Hainan 570228, China.
³ Research & Development Center of Biorational Pesticide, Shaanxi Research Center of Biopesticide Engineering & Technology, Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Northwest A&F University, Yangling 712100, China. Electronic address: fengjt@nwafu.edu.cn.

PMID: 29137937
DOI: 10.1016/j.bmc.2017.11.003

Abstract

A new concise and facile method was explored to synthesize a collection of new 3-arylidene azetidin-2-ones, which could be regarded as the derivatives of the hybrid scaffold of bioactive natural cinnamamide and heterocycle azetidi-2-one. The structures of the synthesized compounds were characterized by ¹H, ¹³C NMR, and MS; and their antifungal activity were evaluated against Alternaria solani Sorauer. These antifungal data were subjected to a quantitative structure-activity relationship (QSAR) analysis using Codessa software on the basis of the results from B3LYP/6-31G(d,p) quantum calculations. The best regressive model revealed that potentially more active compounds should have low dipole moments and Q_C-min (minimal net atomic charge for a C atom), and high Q_O-max (maximal net atomic charge for an O atom) and Q_N-min (minimal net atomic charge for an N atom). The most potent compound 7k could lead to intracellular accumulation of reactive oxygen species, dissipation of mitochondrial transmembrane potential, and an autophagy-like cell death process in A. solani Sorauer. Taken together, these results laid the foundation for further design of improved crop-protection agents based on this hybrid scaffold.

Keywords: 3-Arylidene azetidin-2-ones; Antifungal activity; QSAR model; Subcellular effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternaria / drug effects*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Azetidines / chemical synthesis
Azetidines / chemistry
Azetidines / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship

Substances

Antifungal Agents
Azetidines