Interactions between Pyrazine Carbazide Compounds with CT-DNA and In Vitro Antibacterial
ZHANG Yuzhen1, LIU Xiangrong1,2*, YANG Zaiwen1,2, ZHAO Shunsheng1,2
1. College of chemistry and chemical engineering, Xi'an University of science and technology, Xi'an 710054, China; 2. Key Laboratory of Coal Resources Exploration and Comprehensive Utilization of MNR, Xi'an 710021, China
Abstract：Three novel pyrazine carbazide compounds C13H14N6O(a), C13H14N6O2(b) and C12H12N6O2(c) were synthesized from methyl 5-chloropyrazine-2-carboxylate and hydrazine hydrate by nucleophilic substitution and dehydration condensation reaction. Compounds a~c were characterized by elemental analysis and 1H NMR, which indicated the synthesized products were the target compounds. The single crystal of compound a was obtained by solvent evaporation method, and its crystal structure was determined to be monoclinic by X-ray single crystal diffraction. According to the UV-vis spectroscopy, compounds a~c interacted with CT-DNA in an insertion mode. Interactions between compounds a~c and CT-DNA were measured by microcalorimetric experiment. It was found that the reaction processes were exothermic, the thermal effects ΔH were -5.77×103, -5.50×103 and -5.96×103 kJ·moL-1 respectively, and the reaction time were less than 40 min. The results of the molecular docking simulation calculation showed that the specific binding sites of compounds a and b interacting with DNA included A-chain DC4 and DG5 as well as B-chain DC4, DG5 and DA6, the binding sites of compound c interacting with DNA included A-chain DC4 and DG5 as well as B-chain DC4 and DG5. The antibacterial activities of compounds a~c against B. subtilis, S. aureus, P. aeruginosa and E. coli were determined by Oxford cup method, and the results displayed that compounds a~c all exhibited better antibacterial activities against P. aeruginosa than the positive control tetracycline.
