Fungicidal activity of novel quinazolin-6-ylcarboxylates and mode of action on Botrytis cinerea.

BACKGROUND: Fungal diseases remain important causes of crop failure and economic losses. As the resistance toward current selective fungicides becomes increasingly problematic, it is necessary to develop efficient fungicides with novel chemotypes. RESULTS: A series of novel quinazolin-6-ylcarboxylates which combined the structures of pyridine or heterocyclic motif and the N-(3-chloro-4-fluorophenyl)quinazolin-4-amine moiety, a binding group of ATP-binding site of gefitinib, were evaluated for their fungicidal activity on different phytopathogenic fungi. Most of these compounds showed excellent fungicidal activities against Botrytis cinerea and Exserohilum rostratum, especially compound F17 displayed the highest activity with EC50 values as 3.79 µg mL-1 against B. cinerea and 2.90 µg mL-1 against E. rostratum, which was similar to or even better than those of the commercial fungicides, such as pyraclostrobin (EC50 , 3.68, 17.38 µg mL-1 ) and hymexazol (EC50 , 4.56, 2.13 µg mL-1 ). Moreover, compound F17 significantly arrested the lesion expansion of B. cinerea infection on tomato detached leaves and strongly suppressed grey mold disease on tomato seedlings in greenhouse. The abilities of compound F17 to induce cell apoptosis of the non-germinated spores, to limit oxalic acid production, to reduce malate dehydrogenase (MDH) expression, and to block the active pocket of MDH protein were demonstrated in B. cinerea. CONCLUSION: The novel quinazolin-6-ylcarboxylates containing ATP-binding site-directed moiety, especially compound F17, could be developed as a potential fungicidal candidate for further study. © 2023 Society of Chemical Industry.

The effect of α-tocopherol and dithiothreitol in ameliorating emamectin benzoate cytotoxicity in human K562 cells involving the modulation of ROS accumulation and NF-κB signaling.

Emamectin benzoate (EMB) toxicity contributes a potential risk to environment and human health. To investigate the effect of α-tocopherol (VitE) and dithiothreitol (DTT) in ameliorating EMB-induced cytotoxicity in human K562 cells, in vitro cultured human K562 cells were incubated with different concentrations of EMB in supplement with VitE and DTT when the cells were in the logarithmic phase. Next, the cell growth inhibition was evaluated using the MTT assay and cellular morphology observation. Reactive oxygen species (ROS) production was monitored using DCFH-DA probe and NF-κB signaling was determined using Western blotting. The results demonstrated that treatment with EMB (time- and concentration-dependent) showed significantly greater inhibition on K562 cell viability, heavier chromatin condensation and DNA fragmentation, and stronger suppression of NF-κB/p105 and p65/RelA expression of K562 cells than the control group (p < 0.01). The supplementation of VitE or DTT could help protect K562 cells against EMB-induced cytotoxicity by improving cell viability, preventing ROS accumulation and up-regulating NF-κB signaling through their ameliorating effects against oxidative stress induced by EMB. VitE had a stronger synergistic effect in limiting EMB cytotoxicity than DTT. Our findings indicate that VitE and DTT are potent antioxidants for human K562 cells, offering a promising means of ameliorating EMB cytotoxicity.

Apoptosis of leukemia K562 and Molt-4 cells induced by emamectin benzoate involving mitochondrial membrane potential loss and intracellular Ca2+ modulation.

Leukemia threatens millions of people's health and lives, and the pesticide-induced leukemia has been increasingly concerned because of the etiologic exposure. In this paper, cytotoxic effect of emamectin benzoate (EMB), an excellent natural-product insecticide, was evaluated through monitoring cell viability, cell apoptosis, mitochondrial membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in leukemia K562 and Molt-4 cells. Following the exposure to EMB, cell viability was decreased and positive apoptosis of K562 and Molt-4 cells was increased in a concentration- and time- dependent fashion. In the treatment of 10µM EMB, apoptotic cells accounted for 93.0% to K562 cells and 98.9% to Molt-4 cells based on the control, meanwhile, 63.47% of K562 cells and 81.15% of Molt-4 cells exhibited late apoptotic and necrotic features with damaged cytoplasmic membrane. 48h exposure to 10µM EMB increased significantly the great number of cells with mitochondrial membrane potential (MMP) loss, and the elevation of [Ca2+]i level was peaked and persisted within 70s in K562 cells whilst 50s in Molt-4 cells. Moreover, a stronger cytotoxicity of EMB was further observed than that of imatinib. The results authenticate the efficacious effect of EMB as a potential anti-leukemia agent and an inconsistency with regard to insecticide-induced leukemia.