Synthesis and Biological Evaluation of Benzofuroxan Derivatives as Fungicides against Phytopathogenic Fungi

Abstract

Forty-four benzofuroxan derivatives were designed and prepared as antifungal agents. Their structures were characterized by (1)H NMR, (13)C NMR, and HRMS. Their antifungal activities were tested in vitro with four important phytopathogenic fungi, namely, Rhizoctonia solani , Sclerotinia sclerotiorum , Fusarium graminearum and Phytophthora capsici , using the mycelium growth inhibition method. Compound A5 displayed the maximum antifungal activity against F. graminearum (IC50 = 1.1 μg/mL, which is about 2-fold higher than that of the well-known positive control carbendazim (IC50 = 0.5 μg/mL). A14 exhibited high antifungal effect against both S. sclerotiorum and F. graminearum Sehw., with IC50 values of 2.52 and 3.42 μg/mL, respectively. Among 14 benzofuroxan derivatives with substitutions at the R(2) and R(3) positions of the phenyl ring (B series), 7 compounds displayed strong growth inhibition against R. solani (IC50 ≤ 3.0 μg/mL). Analysis of the structure-activity relationship data of these compounds revealed that (1) introduction of an electron-donating amino group to the R(2) position of the phenyl ring favors antifungal activity against R. solani and (2) the presence of a nitro group at the R(4) position and substituent variation at the R(1) position of the phenyl ring can result in good antifungal candidates against F. graminearum Sehw. Overall, the benzofuroxan was discovered as a novel scaffold for the development of fungicides. Significantly, A14 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo.

A suite of complementary biocontrol traits allows a native consortium of root‐associated bacteria to protect their host plant from a fungal sudden‐wilt disease

“…However, in nature, bacteria interact with plants in multitaxa consortia, systems which remain poorly understood. Pathogenic fungi and bacteria pose a chronic threat to food security (Kobayashi & Crouch, ; Wang, Li, Zhang, Qiao, & Ye, ; Whipps, ). Public concerns over the increasing use of chemicals, which can be environmentally damaging and increase the resistance of fungal phytopathogens, have fuelled renewed interest in the use of microbial biocontrol agents (BCAs) against phytopathogens (Bacon & Hinton, ; Pal & Gardener, ).…”

Gene Cloning, Recombinant Expression, Characterization, and Molecular Modeling of the Glycolytic Enzyme Triosephosphate Isomerase from Fusarium oxysporum

“…Due to the impact of these fungi in the agricultural sector and their medical importance, because it is considered as an emerging and opportunistic group in humans [11], some researchers have studied them through different techniques to understand their physiology and, mainly, their pathogenic mechanisms to find alternatives for their control. The design and chemical synthesis of antifungal molecules have been used as a method to evaluate the inhibition of mycelial growth or to inhibit the activity of specific proteins, as evaluated in F. graminearum [12][13][14]. In recent years, the search for new molecules has been based on the analysis of specific targets such as proteins, of which intracellular signaling proteins, cytoskeleton, membrane, or enzymes that participate in the metabolism have been proposed for the treatment of pathogenic species [15].…”

C-C Coupling Reactions between Benzofurazan Derivatives and 1,3-Diaminobenzenes

“…In the study, the first Wheland intermediate in benzofurazan series was isolated and fully characterized [ 32 ]. Among the mechanistic studies here described, it is noteworthy that benzofuroxans and benzofurazans are interesting reagents from a biological point of view—for example, as fluorescent probes [ 33 , 34 ] or fungicides [ 35 ]. Nitric oxide constitutes a biologically important molecule of the endothelium-derived relaxing factor, and the benzofuroxan moiety is well known for its ability to release NO under physiological conditions [ 36 , 37 ].…”