Inhibition of hippocampal cyclin-dependent kinase 5 activity ameliorates learning and memory dysfunction in a mouse model of bronchopulmonary dysplasia.

AIMS: Oxygen therapy plays a vital role in the development of bronchopulmonary dysplasia (BPD), which is the independent risk factor for neurodevelopment deficits in premature infants. However, the effect of hippocampal cyclin-dependent kinase 5 (CDK5) on BPD-associated neurodevelopment deficits is not fully understood. METHODS: Mice were placed in a hyperoxia chamber from postnatal Day 1 to Day 7. Hematoxylin and eosin staining was used to evaluate the lung histomorphological characteristics. Learning and memory functions of mice were detected by Morris water maze. TUNEL staining was applied to measure the number of apoptotic cells. The expression of CDK5, apoptosis-related protein, and neuroplasticity-related proteins were analyzed by Western blot. Golgi staining was used to assess the structure of dendritic spines. RESULTS: Hyperoxia-induced BPD mice showed a long-term learning and memory dysfunction, more severe neuronal apoptosis, and a decline of synaptic plasticity. Inhibition of CDK5 overactivation ameliorated cognitive deficits, neuronal apoptosis, and synaptic plasticity disorders in BPD mice. CONCLUSIONS: This study first found a vital role of CDK5 in BPD-associated neurodevelopmental disorders. Inhibition of CDK5 overexpression could effectively improve cognitive dysfunctions in BPD mice, which indicated that hippocampal CDK5 may be a new target for prevention and treatment in learning and memory dysfunction of BPD.

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been a good target for herbicide discovery. In order to discover novel HPPD herbicides, a series of pyrazole aromatic ketone analogs were designed and synthesized. RESULTS: The 25 pyrazole aromatic ketone analogs synthesized were tested for herbicidal activity and compounds A1, A3, A4, A17, A20 and A25 displayed excellent herbicidal activity against Chenopodium serotinum, Stellaria media and Brassica juncea at 37.5 g ha-1 . In addition, compounds A1, A5, A9, A10, A16, A17, A20 and A25 exhibited good crop selectivity for wheat, maize and rice at 150 g ha-1 . Inhibition activities against AtHPPD proved the compounds were HPPD inhibitors. The structure-activity relationship of these pyrazole aromatic ketone analogs was studied using molecular docking. CONCLUSION: These pyrazole aromatic ketone derivatives could be used as lead structures for development of HPPD herbicides against dicotyledonous weeds with further structure modification. © 2019 Society of Chemical Industry.

Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity.

BACKGROUND: In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. RESULTS: Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. CONCLUSION: It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.