Ionic Liquids Enhanced Alkynyl Schiff Bases Derivatives of Fipronil Synthesis and Their Cytotoxicity Studies.

Liu Liu,Jin Jin,Yan Yan,Huang Huang,Xu Xu,Li Li,Chen Chen

doi:10.3390/molecules24183223

Abstract

To obtain highly selective toxic derivatives of fipronil, a series of Schiff bases with an alkynyl group (3a–3k) were designed and synthesized from 4-ethynylbenzaldehyde (2) and 4-substituted 5-amino-N-arylpyrazole (1a–1k) via a nucleophilic addition elimination reaction in ionic liquids. Utilization of ionic liquids was demonstrated to endow the yield of each compound beyond 50%, which was enhanced over 1.5 times of the synthetic productive rates comparing the conventional method by which longer reactive time was consumed. The derivatives were characterized via nuclear magnetic resonance hydrogen spectroscopy (1H-NMR), carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), and electrospray ionization high resolution mass spectrometry (ESI-HRMS). The cytotoxicity of these derivatives on Trichoplusia ni (Hi-5) cell and Spodoptera litura cell (SL cell) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) bioassays. The results indicated that several compounds had potential cytotoxicity on Hi-5 cell, especially a 4-ethyl substituted alkynyl Schiff base derivative (3f) that was demonstrated to possess high selective toxicity to the Hi-5 cell than the SL cell. In addition, 3f exhibited comparable toxic activity to commercial fipronil on a Hi-5 cell while a little toxic effect on the SL cell, which satisfied the expectation for selective toxicity screening.

Highlights

Fipronil (I) (Figure 1), with two key functional groups of amino and trifluoromethyl sulfonyl group on its arylpyrazole structure, has special insecticidal activity on soil insects and fleas [1,2,3].it is difficult to avoid the non-specific toxicity toward aquatic invertebrates and non-target organisms such as honeybees, terrestrial game birds, and shrimp [4,5,6]
The results indicated that several compounds had potential cytotoxicity on High 5 Cell lines (Hi-5) cell, especially a 4-ethyl substituted alkynyl Schiff base derivative (3f) that was demonstrated to possess high selective toxicity to the Hi-5 cell than the Spodoptera litura cell (SL cell)
3f exhibited comparable toxic activity to commercial fipronil on a Hi-5 cell while a little toxic effect on the Spodoptera litura cell (SL) cell, which satisfied the expectation for selective toxicity screening

Summary

Introduction

Fipronil (I) (Figure 1), with two key functional groups of amino and trifluoromethyl sulfonyl group on its arylpyrazole structure, has special insecticidal activity on soil insects and fleas [1,2,3].it is difficult to avoid the non-specific toxicity toward aquatic invertebrates and non-target organisms such as honeybees, terrestrial game birds, and shrimp [4,5,6]. Fipronil (I) (Figure 1), with two key functional groups of amino and trifluoromethyl sulfonyl group on its arylpyrazole structure, has special insecticidal activity on soil insects and fleas [1,2,3]. The metabolites derived from fipronil were toxic as well [7,8,9], which would threaten the balance of ecosystems. Fipronil was a restricted application in China and was prohibited from commercial registration in California [10]. Derivation of fipronil to discover compounds with selective toxicity would be an alternative to overcome the dilemma of non-specific toxicity. It is worth to designate, synthesize, and screen fipronil derivatives with selective toxicity

Methods

Results

Conclusion