Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9Cl2N3O, 3 a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9BrClN3O, 3 b) and 4...Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9Cl2N3O, 3 a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9BrClN3O, 3 b) and 4-iodobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9ClIN3O, 3 c), have been synthesized and characterized by elemental analysis, IR, 1 H NMR, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that 3 a^3 c crystallize in monoclinic with space group Cc. The units of 3 a ~ 3 c were linked by intermolecular N–H...X(X = Cl, Br, I) hydrogen bonds into 2 D layered structures, which were further extended into 3 D networks by a series of π-π stacking interactions. Thermogravimetric analysis showed that all of them possessed higher thermal stabilities. The reactivities toward calf thymus DNA(ct-DNA) and bovine serum albumin(BSA) of 3 a^3 c were investigated by UV-vis and fluorescent spectroscopy as well as molecular docking simulation. Both theoretical and experimental results indicated that 3 a^3 c bound to ct-DNA in the mode of minor groove binding, and interacted with BSA through the hydrophobic cavity near TRP213. Besides, the orders of binding affinities of 3 a^3 c to ct-DNA and BSA were both 3 c > 3 b > 3 a, which were the same as that of antibacterial activities. Thus, the interactions of iodinated acylhydrazone with biological targets were stronger than that of chlorinated and brominated acylhydrazones, which provided a representative case for halogenation of lead compounds in rational drug design.展开更多
Three new acylhydrazones containing pyrazine ring(C12H11N5O2·CH3COOH,1;C13H13N5O·2CH3COOH,2;C13H13N5O3·C13H13N5O3,3)were synthesized and fully characterized.The single-crystal XRD indicated that both 1 ...Three new acylhydrazones containing pyrazine ring(C12H11N5O2·CH3COOH,1;C13H13N5O·2CH3COOH,2;C13H13N5O3·C13H13N5O3,3)were synthesized and fully characterized.The single-crystal XRD indicated that both 1 and 2 crystallized in monoclinic,P21/c space group but 3 belonged to monoclinic,C2/c space group.The temperature of the maximum thermal decomposition peaks measured by thermogravimetry for 1~3 is 284,289 and 276℃respectively,all showing better thermal stabilities.The interactions of 1~3 with calf thymus DNA(CT-DNA)and bovine serum albumin(BSA)were studied by UV-Vis absorption spectroscopy and fluorescence spectroscopy,respectively,presenting that 1~3 could bind to CT-DNA via groove binding mode and quench the fluorescence of BSA through static process.Moreover,molecular docking studies of the interactions between 1~3 with DNA/BSA were in good agreement with experimental results.From antimicrobial activities of 1~3 and gentamycin sulfate against Staphylococcus aureus,Escherichia coli and Salmonella typhimurium,it was inferred that 3 had generally stronger antibacterial activity than 1 and 2 and is more active against Staphylococcus aureus than gentamycin sulfate.The cytotoxic tests of 1~3 and etoposide on human lung cancer cells(A549)were carried out by using the MTT method.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21073139 and 21373158)Science and Technology on Combustion and Explosion Laboratory Foundation of Shaanxi(No.6142603010301)。
文摘Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9Cl2N3O, 3 a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9BrClN3O, 3 b) and 4-iodobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9ClIN3O, 3 c), have been synthesized and characterized by elemental analysis, IR, 1 H NMR, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that 3 a^3 c crystallize in monoclinic with space group Cc. The units of 3 a ~ 3 c were linked by intermolecular N–H...X(X = Cl, Br, I) hydrogen bonds into 2 D layered structures, which were further extended into 3 D networks by a series of π-π stacking interactions. Thermogravimetric analysis showed that all of them possessed higher thermal stabilities. The reactivities toward calf thymus DNA(ct-DNA) and bovine serum albumin(BSA) of 3 a^3 c were investigated by UV-vis and fluorescent spectroscopy as well as molecular docking simulation. Both theoretical and experimental results indicated that 3 a^3 c bound to ct-DNA in the mode of minor groove binding, and interacted with BSA through the hydrophobic cavity near TRP213. Besides, the orders of binding affinities of 3 a^3 c to ct-DNA and BSA were both 3 c > 3 b > 3 a, which were the same as that of antibacterial activities. Thus, the interactions of iodinated acylhydrazone with biological targets were stronger than that of chlorinated and brominated acylhydrazones, which provided a representative case for halogenation of lead compounds in rational drug design.
基金supported by the National Natural Science Foundation of China(Nos.U1903033,21073139 and 21373158)Science and Technology on Combustion and Explosion Laboratory Foundation of Shaanxi(No.6142603010301)。
文摘Three new acylhydrazones containing pyrazine ring(C12H11N5O2·CH3COOH,1;C13H13N5O·2CH3COOH,2;C13H13N5O3·C13H13N5O3,3)were synthesized and fully characterized.The single-crystal XRD indicated that both 1 and 2 crystallized in monoclinic,P21/c space group but 3 belonged to monoclinic,C2/c space group.The temperature of the maximum thermal decomposition peaks measured by thermogravimetry for 1~3 is 284,289 and 276℃respectively,all showing better thermal stabilities.The interactions of 1~3 with calf thymus DNA(CT-DNA)and bovine serum albumin(BSA)were studied by UV-Vis absorption spectroscopy and fluorescence spectroscopy,respectively,presenting that 1~3 could bind to CT-DNA via groove binding mode and quench the fluorescence of BSA through static process.Moreover,molecular docking studies of the interactions between 1~3 with DNA/BSA were in good agreement with experimental results.From antimicrobial activities of 1~3 and gentamycin sulfate against Staphylococcus aureus,Escherichia coli and Salmonella typhimurium,it was inferred that 3 had generally stronger antibacterial activity than 1 and 2 and is more active against Staphylococcus aureus than gentamycin sulfate.The cytotoxic tests of 1~3 and etoposide on human lung cancer cells(A549)were carried out by using the MTT method.
