Based on the strategies of receptor structure-guided neonicotinoid design, a series of novel cis-nitenpyram analogues bearing diglycine esters were designed and synthesized. Preliminary bioassays indicated that the insecticidal spectra of the target compounds were expanded compared with our previous work, while all the target compounds presented excellent insecticidal activities against Nilaparvata lugens and Aphis medicagini at 100 mg/L. Among these analogues, 6b showed 100% mortality against Nilaparvata lugens (LC 50 = 0.163 mg/L) and 90% against Aphis medicagini at 4 mg/L. SARs suggested that the insecticidal potency of our designed cis-nitenpyram analogues was dual-controlled by the size and species of the ester groups. The molecular docking simulations revealed that the structural uniqueness of these analogues may lead to a unique molecular recognition and binding mode compared with the previously designed compounds. Introduction of the peptide bond gave rise to more significant hydrogen bonds between the nitenpyram analogues bonding with the amino acid residues of insect nAChRs. The docking results explained the SARs observed in vitro, and shed light on the novel insecticidal mechanism of these cis-nitenpyram analogues.
A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral ( 1 H NMR, IR, and MS) data and the absolute configuration of compound (II 1 ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evalu- ated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II 21 (IC 50=4.7μM for MCF-7 and IC 50=9.3μM for MDA-MB-231), II 33 (IC 50=2.4μM for MCF-7 and IC 50=4.2μM for MDA-MB-231) and II 40 (IC 50=3.3μM for MCF-7 and IC 50 =8.6μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC 50=4.8μM for MCF-7 and IC 50=9.6μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II 33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II 1 , II 6 , II 11 , II 16 , II 23 , II 28, and II 35 were also studied and compound II 28 afforded the highest photoluminescence quantum yield (38%).
PANG ChunChengSUN ChuanWenWANG JingXIAO DiDING LiBU HongFei
