Discovery of Novel Dihydrolipoamide S-Succinyltransferase Inhibitors Based on Fragment Virtual Screening

Abstract

A series of new oxadiazole sulfone derivatives containing an amide moiety was synthesized based on fragment virtual screening to screen high-efficiency antibacterial agents for rice bacterial diseases. All target compounds showed greater bactericidal activity than commercial bactericides. 3-(4-fluorophenyl)-N-((5-(methylsulfonyl)-1,3,4-oxadiazol-2-yl)methyl)acrylamide (10) showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values of 0.36 and 0.53 mg/L, respectively, which were superior to thiodiazole copper (113.38 and 131.54 mg/L) and bismerthiazol (83.07 and 105.90 mg/L). The protective activity of compound 10 against rice bacterial leaf blight and rice bacterial leaf streak was 43.2% and 53.6%, respectively, which was superior to that of JHXJZ (34.1% and 26.4%) and thiodiazole copper (33.0% and 30.2%). The curative activity of compound 10 against rice bacterial leaf blight and rice bacterial leaf streak was 44.5% and 51.7%, respectively, which was superior to that of JHXJZ (32.6% and 24.4%) and thiodiazole copper (27.1% and 28.6%). Moreover, compound 10 might inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola by affecting the extracellular polysaccharides, destroying cell membranes, and inhibiting the enzyme activity of dihydrolipoamide S-succinyltransferase.

Imidazo[1,2‐a]pyridine as a promising scaffold for the development of antibacterial agents

“…Excellent antibacterial activities were found for n = 1 than n = 2/3. In vivo curative and protective activities of 22 h were studied at concentration of 50 mg/L against bacterial blight in rice as 37.0% and 36.8% respectively (Scheme 4) [65].…”

“…3‐substituted imidazo[1,2‐a]pyridine molecules also exhibit a wide range of biological applications along with the maximum antibacterial activity against [ M. tuberculosis] (ATCC‐27294) and several Gram +ve and Gram ‐ve microorganisms like [ E. coli ] (ATCC‐25922), [ S. aureus ] (ATCC‐ 9144), [ K. pneumoniae ] (ATCC‐13883), and [ B. subtilis ] (ATCC‐6051) [64, 65, 68–70, 75, 76].…”

Research Progress of Benzothiazole and Benzoxazole Derivatives in the Discovery of Agricultural Chemicals

“…In global agricultural production, plant diseases, insects, and weed damage are the main causes of crop yield loss [ 1 , 2 ]. Fungi [ 3 , 4 ], bacteria [ 5 , 6 , 7 ], plant viruses [ 8 , 9 ], pests [ 10 , 11 ], weeds [ 12 ], nematodes [ 13 , 14 , 15 , 16 ], and mites [ 17 ] cause huge economic losses to the world’s agriculture every year. At present, the use of agrochemicals is still one of the most effective means to control plant diseases, insects, and grass damage, especially in the management of pest resistance and resistant weeds [ 18 , 19 ].…”

“…More importantly, when pests (such as armyworms [ 20 ], locusts [ 21 ], and walkers [ 22 ]) break out in large areas, the use of highly efficient chemical pesticides is the most effective strategy for rapid pest control [ 23 ]. However, long-term use of traditional agrochemicals will not only pollute the environment but also increase the resistance of pathogens [ 24 ], resulting in more difficult management of plant diseases, insects, and weeds [ 7 , 25 , 26 ]. Therefore, the development of new agrochemicals with unique action mechanisms to replace traditional pesticides is an urgent problem to be solved in the management of plant diseases, pests, and grass diseases.…”

Screening Method and Antibacterial Activity of 1,3,4-Oxadiazole Sulfone Compounds against Citrus Huanglongbing

“…Growth regulators and biological control cannot eliminate C Las, and it is not a long-term or effective strategy to control HLB. The use of chemical antibacterial agents is an effective means to control plant pathogens and increase yield [ 20 , 21 ]. Broad-spectrum antibiotics are often used to eliminate the symptoms of diseased trees.…”