Crystal Structures, ct-DNA/BSA Binding Properties and Antibacterial Activities of Halogenated Pyridyl Hydrazones

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.

Synthesis, Crystal Structures, and Binding Behaviors with CT-DNA/BSA, Antimicrobial and Cytotoxic Activities of Three New Pyrazine Acylhydrazones

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.