Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.
Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.
College of Plant Protection, Jiangsu Key Laboratory of Pesticide Science, Nanjing Agricultural University , Nanjing 210095, People's Republic of China.
Yong-Hao
YH
Ye
Liang
L
Ma
Zhi-Cheng
ZC
Dai
Yu
Y
Xiao
Ying-Ying
YY
Zhang
Dong-Dong
DD
Li
Jian-Xin
JX
Wang
Hai-Liang
HL
Zhu
D001203:Ascomycota / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D025282:Mycelium / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D009536:Niacinamide / Q000737:chemistry / Q000494:pharmacology*; D010935:Plant Diseases / Q000382:microbiology; D012232:Rhizoctonia / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D009536:Niacinamide; D013385:Succinate Dehydrogenase
antifungal activity; nicotinamide; succinate dehydrogenase inhibitors