Gui-Hua Sheng

Inhibition studies of Helicobacter pylori urease with Schiff base copper(II) complexes

Nine new copper(II) complexes derived from various Schiff bases were prepared. They are [Cu2Br2(L1)2] (1), [Cu(L2)2]·2NO3·2CH3OH (2), [Cu(L3)2]·2Br (3), [Cu(L4)2] (4), [Cu2Cl4(L2)2] (5), [Cu2Cl2(L5)2] (6), [CuL6(NCS)] (7), [CuClL6]·CH3OH (8), and [Cu2(L7)2] (9), where L1 is the monoanionic form of 2-chloro-N′-(4-diethylamino-2-hydroxybenzylidene)benzohydrazide (HL1), L2 is the zwitterionic form of 4-methyl-2-((3-morpholinopropylimino)methyl)phenol (L2), L3 is the zwitterionic form of 2-bromo-4-chloro-6-((2-(2-hydroxyethylamino)ethylimino)methyl)phenol (L3), L4 is the monoanionic form of 2-bromo-4-chloro-6-((cyclopentylimino)methyl)phenol (HL4), L5 is the monoanionic form of 2-((cyclopropylimino)methyl)-4-methylphenol (HL5), L6 is the monoanionic form of 4-methyl-2-((pyridin-2-ylmethylimino)methyl)phenol (HL6), and L7 is the dianionic form of N,N′-bis(5-methylsalicylidene)-1,4-diiminobutane (H2L7). The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Cu atoms in complex 1 display square pyramidal coordination, in complex 5 display trigonal bipyramidal coordination, in complex 9 show tetrahedrally distorted square planar coordination, and in the remaining complexes display square planar coordination. Complexes 2, 3, 5, 7 and 8 show effective urease inhibitory activities, with IC50 values of 0.37 ± 1.22, 0.21 ± 0.97, 0.03 ± 0.78, 0.39 ± 0.58 and 0.76 ± 0.95 μM, respectively. Molecular docking study of the complexes with Helicobacter pylori urease was performed. Complex 5 has the most effective activity against urease, with a mixed competitive inhibition mechanism. The complex interacts with the nickel atom of the urease active center, and with the remaining parts of the complex molecule block the entrance of the urease active pocket.

Synthesis, structure, urease inhibitory, and cytotoxic activities of two complexes with protocatechuic acid derivative and phenanthroline

Two complexes, [CuII(L1)(phen)2](ClO4) (1) and [NiII2(L1)2(phen)2(MeOH)2](ClO4)2 (2), with HL1, a ligand derived from protocatechuic acid (=2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid) and phen (=1,10-phenanthroline) were synthesized and characterized by C, H, and N elemental analysis, UV–vis, FT-IR, and single-crystal X-ray diffraction, which revealed that 1 is mononuclear and 2 is dinuclear. Both complexes crystallized in monoclinic space group C2/c. The urease inhibitory activity and in vitro cytotoxic activity of 1 and 2 were tested. The complexes showed strong inhibitory activity against jack bean urease and significantly suppressed the growth of A549, L929, and SW620 cell lines.

Syntheses, Crystal Structures and Antimicrobial Activities of Vanadium(V) Complexes with Similar Tridentate Hydrazone Ligands ①

Two new oxovanadium(V) complexes, [VOL1(OEt)(EtOH)] (1) and [VOL2(OMe)(MeOH)] (2), were prepared by reaction of [VO(acac)2] (where acac = acetylacetonate) with N′-(3-bromo-2-hydroxybenzylidene)-4-methylbenzohydrazide (H2L1) in ethanol and N′-(3-bromo-2-hydroxybenzylidene)-4-methoxybenzohydrazide (H2L2) in methanol, respectively. Crystal and molecular structures of the complexes were determined by elemental analysis, infrared spectra, and single-crystal X-ray diffraction. The V ions have octahedral coordination. Thermal stability and the inhibition of urease of the complexes were studied. Graphical Abstract

Synthesis, structure, and urease inhibitory activities of three binuclear copper(II) complexes with protocatechuic acid derivative

Three Cu(II) complexes, [CuII2(L1)4(L2)2] (1), [CuII2(L1)4(H2O)2]·HL (2), and [CuII2(L1)3(L3)2]ClO4 (3), with a ligand derived from protocatechuic acid (HL1 = C9H8O4=2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid, L2 = C7H9N=o-toluidine, L3 = C6H16N2=N,N-diethylethylenediamine) were synthesized and characterized by C, H, and N elemental analysis and single-crystal X-ray diffraction, which revealed that the three complexes have similar binuclear structures. Complexes 1 and 3 crystallized in triclinic space group P-1 and 2 in orthorhombic space group P212121. The urease inhibitory activities of the three complexes were tested. All three complexes showed strong inhibitory activity against jack bean urease with an IC50 value of 6.8, 5.5, and 3.5 μM compared with the acetohydroxamic acid (IC50 = 7.5 μM), which was a positive control. Graphical Abstract

Structure and urease inhibitory activity of copper(II) complex with (E)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylic acid

A new caffeic acid derivative ((E)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylic acid, HL1)) is synthesized from caffeic acid, followed by the preparation of a Cu(II) complex, [Cu2(L1)4DMSO2]·2DMSO. The structure is determined by single crystal X-ray diffraction, and the urease inhibitory activity of the complex is studied. The results show that IC50 of the complex is 0.56 μmol/L, which is superior to positive control acetohydroxamic acid (AHA, IC50 was 10.95 μmol/l), i.e., the complex has strong inhibitory activity towards urease.

Synthesis, structure, and urease inhibitory activities of Co(III), Mn(II) and Zn(II) complexes with hydrazone derived from protocatechuic acid

Abstract [CoIII(L1)2·H2O]NO3 (1), [MnII(L1)2·H2O] (2), and [ZnII(L1)2·H2O] (3) with a hydrazone derived from protocatechuic acid (HL1 = C15H13N3O3) were designed, synthesized, and characterized by C, H, N elemental analyses, single-crystal X-ray diffraction, and IR spectra, which revealed that the three complexes are similar structures. Docking study has been done. The urease inhibitory activities of the three complexes were tested. Complexes 1 and 3 showed strong inhibitory activity against jack bean urease with IC50 values of 45.9 and 11.64 μM. Complex 2 had no obvious inhibitory activity to urease; the IC50 was > 50 μM.

Synthesis, crystal structure, and Helicobacter pylori urease inhibition of a dicyanoamide bridged Cu(I/II) complex

Abstract A dicyanoamide-bridged polymeric copper(I/II) complex, [CuII(sal)(bipy)CuI(dca)2]n, was prepared by reaction of 5-methylchlorosalicylaldehyde (Hsal), 2,2′-bipyridine (bipy), sodium dicyanoamide (Nadca), and copper perchlorate in methanol. The complex was characterized by elemental analyses, infrared and electronic spectroscopy, and single-crystal X-ray determination. CuII has a square pyramidal coordination, and CuI has triangular coordination. The complex showed high urease inhibitory activity with IC50 value of 0.16 ± 0.23 μM.

Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents

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.

Synthesis and Crystal Structure of a μ-Oxido-Bridged Dinuclear Iron(III) Complex Derived From 3, 5-Dichlorosalicylaldehyde and 4-(2-Aminoethyl)morpholine

A μ-oxido-bridged dinuclear iron(III) complex, [Fe2O(L1)2(L2)2], where L1 and L2 are the deprotonated forms of 2,4-dichloro-6-[(2-morpholin-4-ylethylimino)methyl]phenol and 3,5-dichlorosalicylaldehyde, respectively, has been prepared and characterized by elemental analysis, infrared spectrum, and single-crystal X-ray determination. The complex crystallizes in the triclinic space group P, with unit cell dimensions a = 10.670(1) Å, b = 11.585(1) Å, c = 19.748(2) Å, α = 86.766(2)°, β = 85.038(2)°, γ = 73.973(2)°, V = 2336.1(4) Å3, Z = 2, GOOF = 1.019, R1 = 0.0422, and wR2 = 0.1024. Structural analysis shows that the iron atoms in the complex are hexacoordinate with a normal Fe-O-Fe bridging angle of 150.84(13)°. Each Fe atom is coordinated by the NNO donor atoms of L1, OO donor atoms of L2, and one bridging O atom. The Fe· · ·Fe distance is 3.467(2) Å.

Synthesis, crystal structure, and urease inhibition of [N′-(3,5-dibromo-2-hydroxybenzylidene)isonicotinohydrazido]-(benzohydroxamato)oxovanadium(V)

A new oxovanadium(V) complex [VOL(BZH)] was prepared by the reaction of [VO(Acac)2] (Acac = acetylacetonate) with N′-(3,5-dibromo-2-hydroxybenzylidene)isonicotinohydrazide (H2L) and benzohydroxamic acid (HBZH) in methanol. Crystal and molecular structure of the complex was determined by elemental analysis, infrared spectra and single crystal X-ray diffraction. The complex crystallizes in the monoclinic space group P21/c, with unit cell dimensions a = 11.424(1), b = 12.012(1), c = 19.565(2) Å, β = 93.487(3)°, V = 2679.8(4) Å3, Z = 4, GOOF = 1.152, R1 = 0.0593, and wR2 = 0.1942. The V atom is in octahedral coordination. Thermal stability and the inhibition of urease of the complex were studied.