ABSTRACT
Three new oxidovanadium(V) complexes were designed, synthesized and characterized by C, H, N elemental analysis, single crystal X-ray diffractionï¼UV/Vis and IR spectra. Complex 1: [VOL1X] (H2L1â¯=â¯(E)-N'-(2-hydroxybenzylidene)-3-methbenzohydrazide, HXâ¯=â¯ethylmaltolâ¯=â¯2-ethyl-3-hydroxy-4-pyrone), Complex 2: [VOL2(CH3O)(CH3OH)], (H2L2â¯=â¯C16H16N2O4â¯=â¯(E)-N'-(2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide, CH3OHâ¯=â¯methanol), Complex 3: [VOL3X] (H2L3â¯=â¯(E)-N'-(3-ethoxy-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide). The insulin-like activity of the three complexes was tested. Both normal and streptozotocin (STZ)-diabetic mice were administered intragastrically for two weeks. It was found that the complexes at doses of 10.0 and 5.0â¯mgâ¯V·kg-1 can significantly decrease the blood glucose level in STZ-diabetic mice, and the blood glucose level in the treated normal mice was not altered. The lesions of kidney and liver caused by diabetes have varying degrees of improvement.
Subject(s)
Coordination Complexes/chemistry , Hydrazones/chemistry , Vanadium/chemistry , Vanadium/pharmacology , Animals , Blood Glucose/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Crystallography, X-Ray , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Molecular Structure , Vanadium/therapeutic useABSTRACT
1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti-inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2/metabolism , Dioxanes/pharmacology , Edema/drug therapy , Piperazines/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Carrageenan , Catalytic Domain/drug effects , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/chemistry , Dioxanes/chemistry , Dose-Response Relationship, Drug , Edema/chemically induced , Humans , Male , Mice , Molecular Docking Simulation , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Rats , Structure-Activity RelationshipABSTRACT
Two new hydrazone compounds, N'-(2-bromobenzylidene)-2-(4-nitrophenoxy)acetohydrazide (1) and N'-(4-nitrobenzylidene)-2-(4-nitrophenoxy)acetohydrazide (2), were prepared and structurally characterized by elemental analysis, IR, UV-Vis and (1)H NMR spectroscopy, and single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic space group P2(1)/n with unit cell dimensions of a = 5.3064(5) Å, b = 18.202(2) Å, c = 15.970(2) Å, ß = 95.866(3)º, V = 1534.4(2) Å(3), Z = 4, R(1) = 0.0457, and wR(2) = 0.0975. Compound 2 crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions of a = 4.6008(7) Å, b = 14.451(2) Å, c = 23.296(3) Å, ß = 93.620(2)º, V = 1545.8(4) Å(3), Z = 4, R(1) = 0.0441, and wR2 = 0.0985. Structures of the compounds are stabilized by hydrogen bonds and π···π interactions. The urease inhibitory activities of the compounds were studied. Both compounds show strong urease inhibitory activities, with IC(50) values of 8.4 and 20.2 µM, respectively.
Subject(s)
Benzylidene Compounds/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Hydrazones/chemical synthesis , Urease/antagonists & inhibitors , Benzylidene Compounds/chemistry , Benzylidene Compounds/pharmacology , Crystallography, X-Ray , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Hydrazones/chemistry , Hydrazones/pharmacology , Molecular Docking SimulationABSTRACT
A novel class of aromatic diacylhydrazine derivatives was designed as PLK1 inhibitors. All the 19 new synthesized compounds were assayed for antitumor activity against the respective cervical cancer cells. In which, nine compounds with better antitumor activities were further tested for their PLK1 inhibitory activity. Last, we have successfully found that compound 7k showed both the promising antitumor activity with IC50 of 0.17 µM against the cervical cancer cells, and also processed the most potent PLK1 inhibitory activity with IC50 of 0.03 µM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and PKL1 (PDB code: 1umw) protein.
