The Biological Activity Research Of Pyrazole Compounds

Background: Pyrazole and its derivatives are a kind of important heterocycliccompounds exhibit a wide range of biological activities, including weeding, insecticidal,antibacterial, antiviral, anticancer, anesthesia, sedation and used as pain killer, etc.Consequently, pyrazole derivatives have been widely used in the field of pesticide andmedicine. Pyrazole compounds belong to nitrogenous organism with good coordinatecharacteristics which demonstrate higher catalytic activity and bioactivity aftercoordinate with metal, especially antimicrobial activity and antitumor activity, whichprovide new insights for designing and synthesising novel antimicrobial and antitumoragents.Objective: To screen6compounds with higher antibacterial activities from26pyrazole compounds. To further explore the effect of these compounds on proliferationand apoptosis of mouse hepatocarcinoma Hca-F, and cytotoxicity of humanhepatocarcinoma HepG2, rat pheochromocytoma PC12and human embryonic kidney293cells. The function-structure association of6kinds of pyrazole derivativesincluding20#(1,4-di[di(4-nitropyrazole-)methyl-]-phenyl),307#(1,4-di[(pyrazole-)-methyl-]-phenyl-CuCl2),143#(1,4-di[(3,5-dimethy-pyrazole-)-methyl-]-phenyl-Zn(SCN)2),144#(1,4-di[(3,5-dimethyl-pyrazole-)-methyl]-phenyl-Cd(SCN)2),98#(1,4-di[(3,5-dimethyl-pyrazol-)-methyl]-phenyl-CuCl2),460#(1,4-di[(3,5-dimethyl-pyrazole-)-methyl]-phenyl-AgN3were also investigated.Methods: The bacteria-inhibiting ring method was applied to measure theantibacterial effects of26pyrazole compounds on the growths of pathogenic bacteria strains of Staphyloccocus aureus, Bacillus subtilis, Escherichia coli, Pseudomonasaeruginosa and Candida albicans. Cell counting kit-8(CCK-8) was used to measure theinfluence of6pyrazole compounds on murine hepatocarcinoma cell line Hca-Fproliferation ability; Hoechst staining was measured to test Hca-F cells apoptosisinduced by6pyrazole compounds; MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2Htetrazolium bromide) assay was performed to evaluate the cytotoxic effect of6pyrazolecompounds on HepG2, PC12and HEK-293cells.Results:1.12pyrazole derivatives isolated from26pyrazole derivatives anddemonstrated antibacterial activities in a dose-dependent manner;2. The6novelpyrazole derivatives with higher antibacterial activities could inhibit Hca-F cellsproliferation. Their inhibitory effect was ordered as:20#>460#>98#>144#>307#>143#;3. The6novel pyrazole derivatives could induce Hca-F cells apoptosis;4. The6novelpyrazole derivatives showed cytotoxicity toward HepG2, PC12and HEK-293cells.Their cytotoxic effect toward HepG2, PC12and HEK-293cells were ordered as:460#>20#>144#>143#>307#>98#,144#>460#>98#>143#>20#>307#and460#>144#>20#>98#>307#>143#, respectively.Conclusion：1. All6novel pyrazole derivatives showed proliferation inhibitionand apoptosis-induce abilities on Hca-F cells;2.20#,98#,143#and144#pyrazolederivatives showed less cytotoxicity on HepG2cells, PC12cells, HEK-293cells;3. Thebiological activities of pyrazole derivatives were closely related to their intrinsicstructures: There biological activities significantly increased by the addition of metalion; The substitution of3,5’-bis(-methyl) increased the electron cloud density ofpyrazole compound which lead to enhance biological activity; The substitution of4’-nitro could reduce the electron cloud density of pyrazole compound which leadto enhance its antibacterial activities against gram positive bacteria; The increaseof pyrazole ring could also improve antibacterial activity of these pyrazole compounds.