Uracil hydrazones: design, synthesis, antimicrobial activities, and putative mode of action.

BACKGROUND: Crop diseases caused by plant pathogenic fungi and bacteria have led to substantial losses in global food production. Chemical pesticides have been widely used as a primary means to mitigate these issues. Nevertheless, the persistent and excessive use of pesticides has resulted in the emergence of microbial resistance. Moreover, the improper application and excessive utilization of pesticides can contribute to environmental pollution and the persistence of pesticide residues. Consequently, the development of novel and highly effective bactericides and fungicides to combat plant pathogens holds immense practical importance. RESULTS: A series of uracil hydrazones IV-B was deliberately designed and evaluated for their antimicrobial efficacy. The results of bioassays indicated that most IV-B exhibited >80% inhibition against the fungal species Monilia fructigena and Sclerotium rolfsii, as well as the bacterial species Clavibacter michiganensis subsp. michiganensis, Xanthomonas oryzae pv. oryzae, and Ralstonia solanacearum, at 50 µg/mL in vitro. In vivo, IV-B20 showed 89.9% of curative and 71.8% of protective activities against C. michiganensis subsp. michiganensis at 100 µg/mL superior to thiodiazole copper and copper hydroxide. IV-B20 also showed excellent protective activity against M. fructigena (96.3% at 200 µg/mL) and S. rolfsii (80.4% at 1000 µg/mL), which were greater than chlorothalonil and equivalent to thifluzamide. Mechanistic studies revealed that IV-B20 induced oxidative damage in pathogenic bacteria and promoted the leakage of cellular contents. CONCLUSION: This study suggests that IV-B20 with uracil hydrazone skeleton has great potential as an antimicrobial candidate. These findings lay a foundation for practical application in agriculture. © 2023 Society of Chemical Industry.

Design, synthesis, high algicidal potency, and putative mode of action of new 2-cyclopropyl-4-aminopyrimidine hydrazones.

Control of cyanobacteria harmful algal blooms remains a global challenge. In the present study, a series of novel 2-cyclopropyl-4-aminopyrimidine hydrazones were designed and synthesized as potential algicides. Compounds 4a, 4b, 4h, 4j, 4k, 4l, and 4m showed potent inhibition against Synechocystis sp. PCC6803 (median effective concentration, EC50 = 1.1 to 1.7 µM) and Microcystis aeruginosa FACHB905 (EC50 = 1.2 to 2.0 µM), more potent than, or comparably with, copper sulfate (PCC6803, EC50 = 1.8 µM; FACHB905, EC50 = 2.2 µM) and prometryne (PCC6803, EC50 = 12.3 µM; FACHB905, EC50 = 7.2 µM). Compound 4k exhibited algicidal activity in an expanded culture system, and was less toxic than copper sulfate to zebrafish. Electron microscope analyses showed that 4k damaged cyanobacterial cells and decreased the number of thylakoid lamellae. Transcriptomic and qPCR analyses suggest that 4k interfered photosynthesis-related pathways. Treatment with 4k significantly decreased the maximum quantum yield of photosystem II and the photosynthetic electron transfer rate, and the resulting reactive oxygen species damaged thylakoid membranes and photosystem I. The results suggest that 4k is a potential lead for further development of effective and safe algicides.