Heterocycle-Substituted α-Methylene-γ-Butyrolactones Derivatives Synthesis, Antifungal Activity, and 3D-QSAR

Abstract

Developing fungicides from active botanical skeletons is one of the effective methods to tackle the resistance of plant pathogens. Based on our previous discoveries, a series of novel α-methylene-γ-butyrolactone (MBL) derivatives containing heterocycles and phenyl rings were designed according to the antifungal molecule carabrone first discovered in plant Carpesium macrocephalum. The target compounds were synthesized, and the inhibitory activity against pathogenic fungi as well as the mechanism of action were then systematically investigated. Several compounds showed promising inhibitory activities against a variety of fungi. The most potent compound 38 exhibited the EC50 value of 0.50 mg/L against Valsa mali (V. mali), which was more effective than that of commercial fungicide famoxadone. The protective effect of compound 38 against V. mali on apple twigs was superior to that of famoxadone, with an inhibition rate of 47.9% at 50 mg/L. The physiological and biochemical results showed that compound 38 inhibits V. mali by causing cell deformation and contraction, reducing the number of intracellular mitochondria, thickening the cell wall, as well as increasing the permeability of the cell membrane. Based on three-dimensional quantitative structure–activity relationship (3D-QSAR) analyses, it was shown that the introduction of the bulky and negatively charged groups favored the antifungal activity of the novel MBL derivatives. These findings suggest that compound 38 can be a potential candidate for novel fungicides worthy of further investigation further.

Design, Synthesis, and Antifungal Evaluation of Diverse Heterocyclic Hydrazide Derivatives as Potential Succinate Dehydrogenase Inhibitors

“…Electrospray ionization mass spectrometry (ESI− MS) data were acquired using a Waters Xevo TQ-S micro spectrometer. 1 H nuclear magnetic resonance (NMR) spectra were recorded utilizing a JNM-ECZ500R (500 MHz) instrument with dimethyl sulfoxide-d 6 (DMSO-d 6 ) as the solvent and tetramethylsilane (TMS) as the internal standard. The crystal structure was determined using a Bruker APEX-II charge-coupled device (CCD) diffraction instrument.…”

“…Pathogenic fungi infections are one of the most destructive plant diseases that can significantly reduce the quality and yield of food crops. − Most of the existing fungicides can achieve control of pathogenic fungi, but as a result of long-term unreasonable use, pathogenic fungi have developed serious drug resistance. In addition, some commercial products displayed side effects to the beneficial microorganisms.…”

Design, Synthesis and Antifungal Activity of Nootkatone Derivatives Containing Acylhydrazone and Oxime Ester

“…[1,2,3] Over the past few decades, traditional chemical fungicides have been widely used to improve agricultural production and ensure food security, but many have been limited by toxic residues, disease recurrence and pathogen resistance. [4,5] The drug combination was effective strategies to intensify treatment, such as combining the antifungal drug amphotericin B with GSTs (Glutathione S-transferases). [6] The utilization of plantderived fungicides is currently a prominent and burgeoning area in the field of anti-plant pathogen development, owing to their inherent advantages such as natural degradation, low resistance potential, high selectivity, and safety for both humans and animals.…”