姜黄素吡唑衍生物合成及体外抗氧化作用研究  

Study on Synthesis and Antioxidant Activities in Vitro ofCurcumin Pyrazole Derivative

作　　者：张华君 李灿明 眭沁雪 詹美琪 龚晶 朱丽萍 王涛[1] ZHANG Hua-Jun;LI Can-Ming;SUI Qin-Xue;ZHAN Mei-Qi;GONG Jing;ZHU Li-Ping;WANG Tao(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《广州中医药大学学报》2024年第9期2452-2456,共5页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广州中医药大学“双一流”与高水平建设项目(编号:2021xk87,[2022]97号)。

摘　　要：【目的】基于构-效关系,针对二酮位点与苄基肼构建姜黄素吡唑衍生物,并通过探究其抗氧化活性,为姜黄素类抗氧化衍生物的研发提供实验依据。【方法】以姜黄素和苄基肼为起始原料合成姜黄素-N-取代吡唑衍生物,利用红外光谱(IR)、核磁共振(1HNMR,13CNMR)和液-质联用对该衍生物结构进行确证;检测姜黄素及其吡唑衍生物的2,2-联苯基-1-苦基肼(DPPH)自由基清除能力、2,2’-联氮-双-(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)自由基清除能力,评价该衍生物体外抗氧化活性。【结果】成功合成姜黄素吡唑衍生物,姜黄素及其吡唑衍生物分别在4.6~73.6、6.25~100μg·mL^(-1)范围内均呈良好的自由基清除效应,并具有明显量-效关系。DPPH法测定的姜黄素及其吡唑衍生物的半数抑制浓度(IC_(50))值分别是14.24、40.37μg·mL^(-1),而ABTS法测定的姜黄素及其吡唑衍生物的IC_(50)值分别是36.65、19.26μg·mL^(-1)。【结论】姜黄素母体二酮通过吡唑环的替换,抗氧化活性仍旧保留,姜黄素吡唑衍生物作为一种潜在的抗氧化剂值得进一步研究。Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100μg·mL^(-1),respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC_(50))values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37μg·mL^(-1),respectively,while the IC_(50)values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26μg·mL^(-1),respectively.Conclusion The antioxidant activity ofβ-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

关 键 词：姜黄素 吡唑衍生物 苄基肼 抗氧化 生物合成 

分 类 号：R914.5[医药卫生—药物化学]