**Background**
Fungal infections in crops can lead to significant agricultural losses, necessitating the development of potent antifungal agents. Among these, dinitroaniline fungicides are utilized for their broad-spectrum activity against various plant pathogens. Beyond agriculture, the study of these compounds in mammalian and aquatic models provides critical insights into mitochondrial dysfunction and cellular toxicity. Understanding how these agents induce oxidative stress and programmed cell death is essential for evaluating both their efficacy and their environmental impact. In this context, we will introduce a dinitroaniline fungicide – Fluazinam.
**Definition**
Fluazinam is an orally active dinitroaniline fungicide that targets mitochondrial complex I to induce cytotoxicity and antifungal activity. According to the Fluazinam description, it acts by impairing oxidative phosphorylation and triggering various cell death pathways.
**In Vitro and In Vivo Studies**
The Fluazinam biological activity has been extensively characterized across multiple models. In vitro studies using SH-SY5Y cells demonstrated that Fluazinam (0-5 μM; 24 h) induces cell death and nuclear damage. Western blot analysis revealed that Fluazinam (1.25-5 μM) induces the phosphorylation of JNK, activates the p38 pathway, decreases Bcl-2 protein levels, and activates caspase-3 in a dose-dependent manner, while simultaneously decreasing complex I activity. Regarding its antifungal properties, Fluazinam (10-20 μg/mL) shows high control efficiency against B. maydis on detached corn leaves, and exhibits strong activity against F. fujikuroi, with EC50 values for mycelial growth inhibition ranging from 0.0621 to 0.5446 μg/mL across 103 isolates. Furthermore, Fluazinam (0.01-0.5 μM) impairs oxidative phosphorylation in zebrafish larvae, and concentrations of 0.03-0.40 mg/L exhibit acute toxicity to Brachydanio rerio.
Fluazinam in vivo research indicates significant toxicity in non-target species. Oral exposure to Fluazinam (0.5-2.5 mg a.i. mL⁻¹; 24 h) in Partamona helleri worker bees results in reduced food consumption, damage to the midgut epithelium, and the induction of oxidative stress. Notably, this exposure increases Fluazinam Autophagy and apoptosis within the midgut and alters walking behavior. In conclusion, Fluazinam is a potent dinitroaniline fungicide with strong antifungal activity and significant mitochondrial-mediated cytotoxic effects.
Keywords
Fluazinam, 79622-59-6, Fungal, JNK, p38 MAPK, Bcl-2 Family, Caspase, Autophagy, Apoptosis, c-Jun N-terminal kinase, worker bees, zebrafish, F. fujikuroi, antifungal, Inhibitor
References
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[3] Chen YL, et al. Activity of the dinitroaniline fungicide fluazinam against Bipolaris maydis. Pestic Biochem Physiol. 2018 Jun;148:8-15.
[4] Qu XP, et al. Effects of the dinitroaniline fungicide fluazinam on Fusarium fujikuroi and rice. Pestic Biochem Physiol. 2018 Nov;152:98-105.
[5] Wang XH, et al. Fluazinam impairs oxidative phosphorylation and induces hyper/hypo-activity in a dose specific manner in zebrafish larvae. Chemosphere. 2018 Nov;210:633-644.
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[7] Gomes DS, et al. Acute exposure to fungicide fluazinam induces cell death in the midgut, oxidative stress and alters behavior of the stingless bee Partamona helleri (Hymenoptera: Apidae). Ecotoxicol Environ Saf. 2024 Sep 1;282:116677.