Synthesis and antifungal activities of novel nicotinamide derivatives containing 1,3,4-oxadiazole

Abstract

BackgroundPant diseases in agriculture are extremely difficult to control, which bring about for billions of dollars in economic losses worldwide each year; Nicotinamide derivatives has attracted more and more attention in the field of pesticide due to their broad bioactivities. In an effort to discover new molecules with good antifungal activity, a series of nicotinamide derivatives containing 1,3,4-oxadiazole were synthesized and bio-assayed.ResultsBioassays demonstrated that some of the title compounds exhibited favorable antifungal activities against Gibberella zeae, Fusarium oxysporum, and Cytospora mandshurica. compounds 7b, 7c, 8, 9a, 9b, and 9c displayed 46.4%, 39.6%, 53.0%, 43.2%, 58.3%, 45.6% activities against G. Zeae, respectively; the activities of compounds 7a, 7b, 8, 9a, 9b, and 9c against F. oxysporum were 55.2%, 51.1%, 58.9%, 63.2%, 53.3%, and 47.6%, respectively; whereas inhibitory rates of compounds 7a, 7b, 7c, 8, 9a, 9b, and 9c on C. mandshurica were 53.1%, 49.9%, 44.9%, 52.8%, 59.8%, 54.5%, and 49.3%, respectively.ConclusionA series of the novel nicotinamide derivatives containing 1,3,4-oxadiazole were synthesized and bio-assayed. The results of antifungal tests revealed that the synthesized nicotinamide derivatives possessed weakly to moderately antifungal activities against G. zeae, F. oxysporum, and C. mandshurica. Most of the synthesized compounds exhibited similar activities as (or higher than) these of hymexozol on their corresponding fungus, and compounds 7a, 8, 9a, and 9b showed considerable prospects for further optimization. Primary structure-activity relationships revealed that the introduction of the groups of 4-chloro-6-methyl on benzene, the hydrazone group containing N,N-dimethylamino, and acetyl at -NH2 could enhance the antifungal activity.

Design, synthesis, insecticidal activity and 3D-QSR study for novel trifluoromethyl pyridine derivatives containing an 1,3,4-oxadiazole moiety

“…[10][11][12][13][14][15][16] Such as sulfoxaor, a representative commercial insecticide, and was industrialized by Dow Agroscience. 16 1,3,4-Oxadiazole derivative is a highly active pharmacophore and widely was used in pesticide molecules, 17 many active substance containing such a scaffold have been reported as insecticides, [18][19][20][21][22][23][24] fungicides, [25][26][27][28][29][30][31] and herbicides, 32-34 some of them were treated as a pesticide candidate for further industrialization. 25 Recently, Liu and co-workers reported the 1,3,4-oxadiazole derivative with an anthranilic diamide moiety possessed excellent insecticidal activity against P. xylostella, 20 as well as some insecticidal sarisan analogues with an 1,3,4-oxadiazole scaffold were developed by Guo et al 23,35 And in our recent work, a series of insecticidal 1,3,4-oxadiazole molecules bearing a 3-chloropyridin-2-yl-1H-pyrazole was proposed.…”

Nicotinamide-based diamides derivatives as potential cytotoxic agents: synthesis and biological evaluation

“…The key building blocks ortho-amino aryl acid 1 and 2 were selected as starting materials, and which could be conveniently transferred to the corresponding oxazinone heterocyclic intermediates 3 via a classical heterocyclization reaction [ 13 , 20 , 23 – 25 ] with simple procedures. Then these oxazinones were treated with various amines resulting in the target nicotinamide-based diamides derivatives 4a–k via nucleophilic substitution reaction.…”

“…Recently, many nicotinamide derivatives have been reported for their broad pharmacological properties such as anticancer [ 9 – 11 ], anti-angiogenic [ 9 ], and antinociceptive effect [ 12 ] etc. Meanwhile, some nicotinamide derivatives have also been developed as agrochemicals for their insecticidal, herbicidal, and fungicidal activities [ 13 – 18 ]. In addition, many diamides derivatives have been investigated for their wide range of pharmacological activities including antitumor [ 19 , 20 ], anti-inflammatory activities, Factor Xa inhibitors [ 21 ], CCK1 receptor antagonists [ 22 ], and insecticidal and fungicidal activities [ 23 – 25 ] etc., and which all demonstrated this diamide scaffold might be an important pharmacophore for drug discovery.…”

A Rapid Microwave Induced Synthesis of Isonicotinamide Derivatives and their Antifungal Activity

“…The bioassay results have shown that some of them exhibited excellent antifungal activities. [23][24][25][26][27][28] It has been proven that pyridine carboxamide group display fungicidal activity by disrupting the mitochondrial tricarboxylic acid cycle (TCA) through inhibition of the succinate dehydrogenase (SDH) enzyme, also called succinate ubiquinone oxidoreductase (SQR). [29] The most of fungicides are heterocyclic toxic substances which selectively destroy fungal phytopatho-gens ( Figure 1).…”