Novel 1,3,4-Oxadiazole-2-carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase

Abstract

A novel simple 1,3,4-oxadiazole-2-carbohydrazide was reported to discover low-cost and versatile antifungal agents. Bioassay results suggested that a majority of the designed compounds were extremely bioactive against four types of fungi and two kinds of oomycetes. This extreme bioactivity was highlighted by the applausive inhibitory effects of compounds 4b, 4h, 5c, 5g, 5h, 5i, 5m, 5p, 5t, and 5v against Gibberella zeae, affording EC 50 values ranging from 0.486 to 0.799 μg/mL, which were superior to that of fluopyram (2.96 μg/mL) and comparable to those of carbendazim (0.947 μg/mL) and prochloraz (0.570 μg/mL). Meanwhile, compounds 4g, 5f, 5i, and 5t showed significant actions against Fusarium oxysporum with EC 50 values of 0.652, 0.706, 0.813, and 0.925 μg/mL, respectively. Pharmacophore exploration suggested that the N′phenyl-1,3,4-oxadiazole-2-carbohydrazide pattern is necessary for the bioactivity. Molecular docking of 5h with succinate dehydrogenase (SDH) indicated that it can completely locate the inside of the binding pocket via hydrogen-bonding and hydrophobic interactions, revealing that this novel framework might target SDH. This result was further verified by the significant inhibitory effect on SDH activity. In addition, scanning electron microscopy patterns were performed to elucidate the anti-G. zeae mechanism. Given these features, this type of framework is a suitable template for future exploration of alternative SDH inhibitors against plant microbial infections.

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

“…In addition, carbohydrazide group can be considered as an ideal and completely competent surrogate for the amide group. [ 16 ] With convenient synthetic methods and excellent chemical/physical characteristics, carbohydrazide units have played a very important role in the field of agricultural chemistry, and also possessed a broad scope of pharmacological and biochemical activities, including insecticidal, [ 17 ] antibacterial, [ 18‐19 ] antiviral, [ 20 ] antitumor, [ 21 ] antimalarial, [ 22 ] antifungal, [ 23‐24 ] anti‐inflammatory, [ 25 ] and other extensive biological and physiological activities. [ 26‐29 ] Carbohydrazide units have received more and more extensive attention and widely used as the frameworks in the molecular design of new antifungal agents.…”

Synthesis, Antimicrobial Activity, and Molecular Docking of Benzoic Hydrazide or Amide Derivatives Containing a 1,2,3‐Triazole Group as Potential SDH Inhibitors

“…Compared with the commercially available SDHIs Azoxystrobin, Boscalid and Fluxapyroxad, the synthesized compounds were screened for their antifungal activities in vitro against B. d., R. s., C. g., G. z. following our previously reported method. [62] The in vivo fungicidal activities of the synthesized compounds against R. s. and G. z. were carried out by Shenyang Sinochem Agrochemicals R&D Co. Ltd.…”

Synthesis of mono and bis-substituted asymmetrical compounds, (1-(pyridin-2-yl)ethylidene)carbonohydrazide and 1-(2'-hydroxybenzylidene)-5-(1'-pyridylethylidene)carbonohydrazone: Structural characterization and antioxidant activity study

“…The compound (1-(pyridin-2-yl)ethylidene)carbonohydrazide (1) was prepared by a condensation reaction of 2acetylpyridine and carbonohydrazide in methanol. The isolated product was used for the synthesis of the compound (1E,5E)-1-(2-hydroxybenzylidene)-5-(1-(pyridin-2-yl)ethylidene)carbono hydrazide (2). Salicylaldehyde and compound 1 were mixed in methanol under reflux (Scheme 1).…”

“…Carbohydrazide and its derivatives have been largely investigated since 1894 when their syntheses were first reported [1]. Carbohydrazide derivatives were used as precursors for the synthesis of various heterocyclic compounds containing nitrogen atom in the cycle and/or in the free arms [2][3][4]. The reactivity as well as the biological properties of these derivatives have been investigated in the past decades for the development of drugs [5,6] or industrial applications [7,8].…”

“…The reactivity as well as the biological properties of these derivatives have been investigated in the past decades for the development of drugs [5,6] or industrial applications [7,8]. They are known to possess a broad spectrum of biological activities such as antioxidant [9], analgesic [10], antiplatelet [11], antifungal [2], antimicrobial [12], anticonvulsant [13], antidepressant [14], anti-inflammatory [15], anti-tubercular [16], anti-HIV [5], anti-diabetic [10,17], and anticancer activities [3,18]. While most of the older work on carbohydrazide Schiff bases focused on their applicability in classical fields, nowadays these systems are increasingly acknowledged as supreme multitopic ligands for the targeted construction of original metal-organic architectures such as grids [19,20].…”