Discovery of Natural Sesquiterpene Lactone 1-O-Acetylbritannilactone Analogues Bearing Oxadiazole, Triazole, or Imidazole Scaffolds for the Development of New Fungicidal Candidates.

In recent decades, natural products have been considered important resources for developing of new agrochemicals because of their novel architectures and multibioactivities. Consequently, herein, 1-O-acetylbritannilactone (ABL), a natural sesquiterpene lactone from Inula britannica L., was used as a lead for further modification to discover fungicidal candidates. Six series of ABL-based derivatives containing an oxadiazole, triazole, or imidazole moiety were designed and synthesized, and their antifungal activities were also evaluated in vitro and in vivo. Bioassay results revealed that compounds 8d, 8h, and 8j (EC50 = 61.4, 30.9, and 12.4 µg/mL, respectively) exhibited more pronounced inhibitory activity against Fusarium oxysporum than their precursor ABL (EC50 > 500 µg/mL) and positive control hymexazol (EC50 = 77.2 µg/mL). Derivatives 8d and 11j (EC50 = 19.6 and 41.5 µg/mL, respectively) exhibited more potent antifungal activity toward Cytospora mandshurica than ABL (EC50 = 68.3 µg/mL). Compound 10 exhibited excellent and broad-spectrum antifungal activity against seven phytopathogenic fungal mycelia. Particularly, the inhibitory activity of compound 10 against the mycelium of Botrytis cinerea was more than 10.8- and 2.3-fold those of ABL and hymexazol, respectively. Meanwhile, derivative 10 (IC50 = 47.7 µg/mL) displayed more pronounced inhibitory activity against the spore of B. cinerea than ABL (IC50 > 500 µg/mL) and difenoconazole (IC50 = 80.8 µg/mL). Additionally, the in vivo control efficacy of compound 10 against B. cinerea was further studied using infected tomatoes (protective effect = 58.4%; therapeutic effect = 48.7%). The preliminary structure-activity relationship analysis suggested that the introduction of the 1,3,4-oxadiazole moiety (especially the 1,3,4-oxadiazole heterocycle containing the 4-chlorophenyl, 2-furyl, or 2-pyridinyl group) on the skeleton of ABL was more likely to produce potential antifungal compounds. These findings pave the way for further design and development of ABL-based derivatives as potential antifungal agents.

Occurrence and risk assessment of currently used organophosphate pesticides in overlying water and surface sediments in Guangzhou urban waterways, China.

Organophosphate pesticides (OPPs) are one type of the most massively used pesticides and ubiquitously detected in aquatic environments, which may pose potential risks to the aquatic organisms and human health. In the present study, the spatiotemporal distribution and potential risks of OPPs were investigated in overlying water and surficial sediments from urban waterways of Guangzhou. For all studied sites, in general, four target OPPs (i.e., malathion, chlorpyrifos, terbufos, and diazinon) were present in the overlying water, with malathion and chlorpyrifos as major components. Higher concentrations of the four OPPs were found for the water and sediments collected in the dry season compared to the wet season, possibly because of the dilution effect of heavy rains. The results of Pearson's analyses and principal coordinate analyses (PCoA) suggested similar sources for target OPPs in the water and sediments across the Guangzhou urban waterways. Potential ecological risks of the OPPs to three representative taxons (algae, aquatic invertebrates, and fish) were evaluated via toxic units (TUs) and risk quotients (RQs), while risk assessment on human health was performed using hazard index (HI). Although TU results showed no acute risks to the aquatic organisms in the overlying water and surface sediments, RQ results of the mixture showed high risks to the aquatic invertebrate and fish in all water samples. Individual HI values and cumulative HI values were on the order of 10-6-10-3 for children and adults, suggesting no potential risks to either children or adults through drinking and bathing.