Synthesis and biological evaluation of benzofuroxan derivatives as fungicides against phytopathogenic fungi.
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.
College of Pharmaceutical Science, Soochow University , Suzhou 215123, Jiangsu, People's Republic of China.
Lili
L
Wang
Cong
C
Li
Yingying
Y
Zhang
Chunhua
C
Qiao
Yonghao
Y
Ye
D001203:Ascomycota / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000138:chemical synthesis* / Q000494:pharmacology*; D005670:Fusarium / Q000187:drug effects; D010838:Phytophthora / Q000187:drug effects; D010935:Plant Diseases / Q000382:microbiology; D010944:Plants / Q000382:microbiology*; D012232:Rhizoctonia / Q000187:drug effects; D013329:Structure-Activity Relationship
D001572:Benzofurans; D005659:Fungicides, Industrial