4-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine Derivatives: Design, Synthesis, Insecticidal Assay and Binding Mode Studies.

A series of 4-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized based on the fipronil low energy conformation by scaffold hopping strategy. Physicochemical properties calculation, insecticidal assay and binding mode studies were also performed. It was found that the target compounds displayed lower insecticidal activities than fipronil. The differences in binding modes between these compounds and fipronil may be the major reason for reduced insecticidal activities.

Insights into pesticide toxicity against aquatic organism: QSTR models on Daphnia Magna.

The toxicities of agrochemicals to non-target aquatic organisms are key items in chemical ecological risk assessment. However, it is still an urgent need to develop new tools to assess the agrochemical aquatic toxicity efficiently and accurately. In this work, QSTR studies were performed on a data set containing 639 diverse pesticides with measured EC50 toxicity against Daphnia magna, by using five machine learning methods combined with seven fingerprints and a set of molecular descriptors. The imbalance problem of the data set was successfully solved by clustering analysis. The top-10 QSTR models displayed greater predicative abilities than ECOSAR. The optimal model, Ext-SVM, showed the best performance in 10-fold cross validation (Qhigh=0.807, Qmoderate=0.806, Qlow=0.755, Qtotal=0.794), and also in the test set verification (Qhigh=0.865, Qmoderate=0.783, Qlow=0.931, Qtotal=0.848). The relevance of the key physical-chemical properties with the toxicity was also investigated, in which the MW, a_np, logP(o/w), GCUT_SLOGP_1, chilv and SMR_VSA7 values displayed positive correlation with Daphnia magna toxicity, whereas the logS and a_don showed negative correlation. The robust QSTR models provided efficient tools for assessing agrochemical aquatic toxicity, and the revealed different physical-chemical properties between the high and low toxic compounds might be useful in the discovery and design of low aquatic toxic pesticides.