3553-93-3Relevant articles and documents
Structure-activity relationships of benzylidene anabaseines in nicotinic acetylcholine receptors of cockroach nerve cords
Sultana, Israt,Ikeda, Izumi,Ozoe, Yoshihisa
, p. 2963 - 2971 (2002)
Ten analogues of 6′-chloro-3-benzylideneanabaseine (CBA) bearing substituents at the ortho- and the para-positions of the phenyl group were synthesized, together with two related compounds. The affinity of the synthesized compounds for nicotinic acetylcholine receptors (nAChRs) in the nerve cord of the American cockroach (Periplaneta americana L.) was examined by the radioligand binding assay using [3H]epibatidine (EPI), a nAChR agonist. All 12 tested compounds inhibited [3H]EPI binding, showing Ki values ranging from 14.6 to 6830 nM. The potency variation of para-substituted CBA analogues was explained by the steric (ΔB1) and electronic (σp) parameters of the para-substituents, or by the steric parameter and the charge of the N1 nitrogen atom (qN1). Among the CBA analogues, only two compounds containing a dimethylamino group and a methoxy group at the para-position showed high insecticidal activity against the German cockroach (Blattella germanica) when injected after pretreatment with metabolic inhibitors. High-affinity analogues of CBA might be suitable probes for use in classifying and characterizing insect nAChR subtypes.
Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo
Zou, Yu,Zhao, Di,Yan, Chang,Ji, Yanpeng,Liu, Jin,Xu, Jinyi,Lai, Yisheng,Tian, Jide,Zhang, Yihua,Huang, Zhangjian
supporting information, p. 1821 - 1832 (2018/03/21)
Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively. Compound 4 possessed 14-fold greater aqueous solubility than 1 and increased ROS levels in colorectal cancer HCT-116 cells. Additionally, 4 preferably inhibited proliferation, migration, invasion, and heteroadhesion of HCT-116 cells. Treatment with 4 suppressed tumor growth and lung metastasis in vivo and prolonged the survival of tumor-bearing mice. Furthermore, 4 mitigated TGF-β1-induced epithelial-mesenchymal transition and Wnt/β-catenin activation by inhibiting the Akt and GSK-3β phosphorylation in HCT-116 cells. Collectively, 4 displayed significant antiproliferation and antimetastasis activities, superior to 1.
Strong influence of intramolecular Si?O proximity on reactivity: Systematic molecular structure, solvolysis, and mechanistic study of cyclic N-trimethylsilyl carboxamide derivatives
Szalay, Roland,Harmat, Veronika,E?ri, János,Pongor, Gábor
supporting information, p. 2186 - 2192 (2017/05/16)
A comparative alcoholysis study of N-silylated derivatives of simple heterocyclic carboxamides (lactams, imides, ureas) is presented. The second-order rate constant values span a range as wide as three orders of magnitude. On the basis of DFT calculations, a good correlation between reactivity and the Si?O distance was found within each family of compounds. The viability of two different reaction pathways was evaluated using a detailed computational mechanistic study of the methanolysis of cyclic urea homologues. Peculiarities in the single-crystal X-ray diffraction structures of the trimethylsilyl and trimethylsiloxy phthalimides are also discussed.
