A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elem...A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elemental analysis. Meanwhile, the single crystal of compound 5 a, C_(19)H_(25)ClN_2 O_3, was also obtained and determined by X-ray crystallography. Crystal data: triclinic system, space group P_1, a = 8.1318(15), b = 11.931(2), c = 12.027(2) ?, α = 67.361(3)°, β = 73.009(3)°, γ = 85.663(3)°, V = 1029.1(3) ?3, Z = 2, F(000) = 388, Dc = 1.178 g/cm3, μ = 0.204 mm^(-1), R = 0.0786 and w R = 0.2212 for 3585 independent reflections(Rint = 0.0214) and 2960 observed ones(I > 2σ(I)). Intermolecular N–H···O stacking interactions contributed to the stability of the structure. The antitumor abilities of 5 were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide(MTT) standard method; 5 c stood out as the most potent showing an IC_(50) of 1.70 μmol/L against human tumor cell lines(HepG2).展开更多
Paris saponinⅦ(PSⅦ),a bioactive constituent extracted from Trillium tschonoskii Maxim.,is cytotoxic to several cancer types.This study was designed to explore whether PSⅦprevents non-small-cell lung cancer(NSCLC)pr...Paris saponinⅦ(PSⅦ),a bioactive constituent extracted from Trillium tschonoskii Maxim.,is cytotoxic to several cancer types.This study was designed to explore whether PSⅦprevents non-small-cell lung cancer(NSCLC)proliferation and to investigate its molecular target.AMP-activated protein kinase(AMPK)has been implicated in the activation of autophagy in distinct tissues.In cultured human NSCLC cell lines,PSⅦinduces autophagy by activating AMPK and inhibiting m TOR signaling.Furthermore,PSⅦ-induced autophagy activation was reversed by the AMPK inhibitor compound C.Computational docking analysis showed that PSⅦdirectly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation.Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSⅦand AMPK.In summary,PSⅦacts as a direct AMPK activator to induce cell autophagy,which inhibits the growth of NSCLC cells.In the future,PSⅦtherapy should be applied to treat patients with NSCLC.展开更多
基金Financial support from the National Natural Science Foundation of China(No.81773746)the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine(No.WDCM009 and 2011JH-2014CXTT07)+1 种基金the Foundation of Health and Family planning Commission of Hubei Province(No.WJ2015Z113)the Foundation for Innovative Research Team of Hubei University of Medicine(2014CXZ01 and 2014CXZ05)
文摘A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elemental analysis. Meanwhile, the single crystal of compound 5 a, C_(19)H_(25)ClN_2 O_3, was also obtained and determined by X-ray crystallography. Crystal data: triclinic system, space group P_1, a = 8.1318(15), b = 11.931(2), c = 12.027(2) ?, α = 67.361(3)°, β = 73.009(3)°, γ = 85.663(3)°, V = 1029.1(3) ?3, Z = 2, F(000) = 388, Dc = 1.178 g/cm3, μ = 0.204 mm^(-1), R = 0.0786 and w R = 0.2212 for 3585 independent reflections(Rint = 0.0214) and 2960 observed ones(I > 2σ(I)). Intermolecular N–H···O stacking interactions contributed to the stability of the structure. The antitumor abilities of 5 were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide(MTT) standard method; 5 c stood out as the most potent showing an IC_(50) of 1.70 μmol/L against human tumor cell lines(HepG2).
基金supported by the National Natural Science Foundation of China(Nos.82072928 and 81802387)the Foundation for Innovative Research Team of Hubei Provincial Department of Education(No.T201915)+4 种基金Hubei Provincial Technology Innovation Project(No.2017ACA176)the Innovative Research Program for Graduates(No.YC2019001)the Principal Investigator Grant of Hubei University of Medicine(No.HBMUPI201806)the Grants of Open Ended Design Project from Hubei Key Laboratory of Wudang Local Chinese Medicine Research(No.WDCM2019008)the Faculty Development Grants from Hubei University of Medicine(Nos.2018QDJZR03 and 2019QDJZR16)。
文摘Paris saponinⅦ(PSⅦ),a bioactive constituent extracted from Trillium tschonoskii Maxim.,is cytotoxic to several cancer types.This study was designed to explore whether PSⅦprevents non-small-cell lung cancer(NSCLC)proliferation and to investigate its molecular target.AMP-activated protein kinase(AMPK)has been implicated in the activation of autophagy in distinct tissues.In cultured human NSCLC cell lines,PSⅦinduces autophagy by activating AMPK and inhibiting m TOR signaling.Furthermore,PSⅦ-induced autophagy activation was reversed by the AMPK inhibitor compound C.Computational docking analysis showed that PSⅦdirectly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation.Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSⅦand AMPK.In summary,PSⅦacts as a direct AMPK activator to induce cell autophagy,which inhibits the growth of NSCLC cells.In the future,PSⅦtherapy should be applied to treat patients with NSCLC.
