CN116375788A - 抗耐碳青霉烯类鲍曼不动杆菌甘草次酸-金配合物及其制备方法和应用 - Google Patents
抗耐碳青霉烯类鲍曼不动杆菌甘草次酸-金配合物及其制备方法和应用 Download PDFInfo
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Abstract
本发明公开了抗耐碳青霉烯类鲍曼不动杆菌甘草次酸‑金配合物及其制备方法和应用。一种甘草次酸‑金配合物,为18α,18β‑甘草次酸和金(Ⅰ)膦的配合物。所述的甘草次酸‑金配合物用于耐碳青霉烯类鲍曼不动杆菌(CRAB)的治疗。本发明通过体外抗菌活性实验,证明本发明制备的甘草次酸‑金配合物不仅对耐碳青霉烯类鲍曼不动杆菌具有很好的杀菌作用,还具有低细胞毒性和低基因毒性,为研发新型抗鲍曼不动杆菌药物提供了良好的前期研究基础,为解决临床上鲍曼不动杆菌的治疗和防控艰难的困境带来了曙光。
Description
技术领域
本发明属于小分子化合物领域,涉及抗耐碳青霉烯类鲍曼不动杆菌甘草次酸-金配合物及其制备方法和应用。
背景技术
鲍曼不动杆菌作为一种非发酵革兰阴性杆菌,广泛存在于医院环境之中,成为医院常见的感染病原菌。目前,全世界各地报道的耐药性菌株感染病例数量不断上升,耐碳青霉烯的鲍曼不动杆菌(CRAB)菌株对于临床上常使用的舒巴坦/头孢哌酮复方制剂的耐药性不断攀升,甚至对作为治疗耐碳青霉烯类肠杆菌科细菌的最后一线的替加环素与多粘菌素也出现了耐药现象。因此,寻找更为有效的、毒副作用低的抗耐碳青霉烯的鲍曼不动杆菌药物是本领域亟待解决的问题。
众多的研究表明,金(Ⅰ)和金(Ⅲ)配合物已被评估为可能的抗菌剂。金配合物的抗菌活性现已被证实不仅仅取决于金的含量,同时与金中心配位的配体有内在关系。但金配合物细胞毒性较大,安全性低限制了其使用。目前尚未见将金配合物用于抗鲍曼不动杆菌的相关报道。
中药甘草具有抗炎、抗菌、保肝等作用。其活性成分甘草次酸,对于多种革兰氏阴性菌、革兰氏阳性菌和耐药菌等都具有抗菌活性。但不同的抗菌药物有不同的抗菌谱,即便是专用于革兰氏阴性菌的抗生素依然只是对部分革兰氏阴性菌具有抑制作用。目前尚未见甘草次酸用于抗鲍曼不动杆菌的相关报道。
发明内容
本发明的目的是针对现有技术的上述不足,提供抗耐碳青霉烯类鲍曼不动杆菌甘草次酸-金配合物。
本发明的另一目的是提供该甘草次酸-金配合物的制备方法。
本发明的又一目的是提供甘草次酸-金配合物的应用。
本发明的目的可通过以下技术方案实现:
一种甘草次酸-金配合物,为18α,18β-甘草次酸和金(Ⅰ)膦的配合物。
作为本发明的一种优选,所述的甘草次酸-金配合物,选自以下任意一种通式所示化合物:
R2选自PPh3、PTA;
R3选自H、取代或为取代的C3-6环烷基,取代或未取代的苯基,取代或未取代的五元或六元杂环基,其中杂原子为N或S,取代基选自C1-3的烷氧基,卤素,硝基。
本发明所述甘草次酸-金配合物的制备方法,合成路线如下:
本发明所述的甘草次酸-金配合物在制备抗革兰氏阴性菌的药物中的应用。
本发明所述的甘草次酸-金配合物在制备抗耐碳青霉烯类鲍曼不动杆菌或制备耐碳青霉烯类鲍曼不动杆菌的药物中的应用。
有益效果:
本发明甘草次酸-金配合物对耐碳青霉烯类鲍曼不动杆菌具有较好的抑菌效果,最低抑菌浓度为5μM。并且优选化合物4-1-2具有低细胞毒性,低基因毒性,制备简单等优点。
附图说明
图1是甘草次酸-金配合物4和7的结构式。
图2是甘草次酸-金配合物4-1-2与ct-DNA的紫外光谱。
图3是甘草次酸-金配合物4-1-2与ct-DNA的荧光光谱。
图4是甘草次酸-金配合物4-1-2的粘度测定。
具体实施方式
下面用具体实施方式对本发明进行详述。应该理解,具体实施方式部分的内容是属于阐释性的,而非限制性的,即不是对本发明内容的任何限制。
定义:
耐碳青霉烯类鲍曼不动杆菌中的耐碳青霉烯类是指:按照CLSI的方法(纸片法或稀释法),用碳青霉烯类抗生素对鲍曼不动杆菌进行测试,得到的结果按CLSI-M100的标准判定为耐药(resistance)。碳青霉烯类抗生素是抗菌谱最广,抗菌活性最强的非典型β-内酰胺抗生素,因其具有对β-内酰胺酶稳定以及毒性低等特点,已经成为治疗严重细菌感染最主要的抗菌药物之一;具有超广谱的、极强的抗菌活性,以及对β-内酰胺酶高度的稳定性。
TLC薄层层析技术,是以涂布于支持板上的支持物作为固定相,以合适的溶剂为流动相,对混合样品进行定性与定量分析、分离和鉴定的一种层析分离技术。
MTT法是利用活细胞线粒体中的琥珀酸脱氢酶能使外源性MTT还原为水不溶性的蓝紫色结晶甲臜,被二甲基亚砜(DMSO)能溶解后,用酶联免疫检测仪在490nm波长处测定其吸光值,可间接反映活细胞数量。
IC50为50%抑制浓度即B/B0=50%时所对应的浓度,半数抑制是用来衡量抗体灵敏度的半数抑制越低,说明抗体的灵敏度越高。
MIC是指最低抑菌浓度,是测量抗菌药物的抗菌活性大小的一个指标,指在体外培养细菌18至24小时后能抑制培养基内病原菌生长的最低药物浓度。
基因毒性是指污染物能直接或间接损伤细胞DNA,产生致突变和致癌作用的程度。
实施例1:甘草次酸-金配合物的合成方法
化合物3的合成方法:
(1)称取化合物1(7.05g,1.0mmol),溴乙炔(2.30g,1.3mmol),碳酸钾(6.23g,3.0mmol),置于50mLN,N-二甲基甲酰胺(DMF)中,氮气保护,过夜室温反应。加入200mL水稀释,用100mL乙酸乙酯萃取四次。用30mL饱和食盐水润洗三次,浓缩,再用无水硫酸钠干燥,过滤,旋干,得粗产物,再过柱层析(乙酸乙酯/石油醚=1:3)纯化得到白色固状化合物2(收率30-78%)。
(2)称取化合物2(492mg,1.0mmol),化合物8(1.3mmol),碳化二亚胺(572mg,1.5mmol),4-二甲氨基吡啶(121mg,0.5mmol),置于100mL二氯甲烷(DCM)中反应,氮气保护,于室温搅拌。反应结束后,再用150mLDCM萃取三次。浓缩后,用无水硫酸钠干燥,过滤,旋干,得粗产物,过柱层析(乙酸乙酯/石油醚=1:3)纯化得到白色固状化合物3(收率20-80%)。
表1配体化合物3结构式及摩尔质量
化合物4的合成方法:
(1)以PPh3为配体的合成方法:称取化合物3(1.0mmol)溶于5mL四氢呋喃(THF)中,氮气置换三次。10min后加入1mLNaHMDS。称取三苯基膦氯金(44mg,1.0mmol),加入反应液中;避光反应,自然升温至室温搅拌。浓缩后,用无水硫酸钠干燥,过滤,旋干,得粗产物,过柱层析(乙酸乙酯/石油醚=1:3)纯化得到白色固状化合物4(收率30-85%)。
(2)以PTA为配体的合成方法:称取化合物3(1.0mmol)溶于10mL二氯甲烷和甲醇混合液(DCM/甲醇=3:1)的溶液中,氮气置换三次。先后加入氢氧化钾(9.1mg,1.2mmol)和5-三氮杂-7-磷杂金刚烷氯金(22mg,1.05mmol)。避光反应,室温搅拌16h,TLC监测反应完全,浓缩后旋干,得粗产物,过柱层析(DCM/甲醇=1:40)纯化得到白色固状化合物4(收率25-80%)。
表2配合物4结构式及摩尔质量
化合物6的通用合成方法:
(1)称取化合物2(1.01g,1.0mmol),置于20mLDCM中,冰浴反应25min。再加入戴斯马丁试剂(1.85g,2.0mmol),室温反应。反应结束后,用无水硫酸钠干燥,过滤,旋干,得粗产物,再过柱层析(乙酸乙酯/石油醚=1:20)纯化,得到白色固体粉末化合物5(收率30-85%)。
(2)称取化合物5(4.71g,1.0mmol),4-氟苯甲醛(3.72g,3.0mmol),氢氧化钾(0.84g,1.5mmol),置于10mL无水乙醇中,室温搅拌。反应结束后,加入100mL水稀释,再用150mLDCM萃取三次。浓缩后,用无水硫酸钠干燥,过柱层析(乙酸乙酯/石油醚=1:3)纯化得到白色固体化合物6(收率25-85%)。
表3配体化合物6结构式
化合物7的通用合成方法同化合物4的合成方法。
表4配合物7结构式
实施例2:甘草次酸-金配合物对人正常肝细胞LO2和人肝癌细胞HepG2的毒性检测
采用MTT法对25种甘草次酸-金配合物进行细胞毒性检测。取对数期人正常肝细胞LO2和人肝癌细胞HepG2,调整细胞悬液浓度至1×104-105个·mL-1,每孔加入100μL,置于5%CO2,37℃培养箱培养12小时。然后,设置6个梯度,分别为20,10,5,2.5,1.25和0.625μg·mL-1,每个浓度设5个复孔,每孔加100μL甘草次酸配合物溶液。将培养板继续置于培养箱中培养16-48小时,倒置显微镜下观察。然后向每孔加入20μLMTT(5mg·mL-1,即0.5%MTT)溶液,继续培养4h。每孔加入150μL二甲基亚砜,置摇床上低速振荡10min。在酶联免疫检测仪OD490nm处测量各孔的吸光值。
结果:11种化合物对LO2和HepG2的IC50(μM)>20(μM),说明其细胞毒性较小(表3)。
实施例3:甘草次酸-金配合物对耐碳青霉烯类鲍曼不动杆菌的体外抗菌活性
对甘草次酸-金配合物进行了抗菌活性和最低抑菌浓度的测定,参照CLSI(美国临床标准协会)M07-A9微量肉汤稀释法。往广口瓶中加入500mL蒸馏水,称取胰蛋白胨5g、酵母浸粉2.50g、NaCl5g溶于蒸馏水中,于高压灭菌锅中121℃灭菌15min,冷却后放置于4℃冰箱中保存使用。细菌接种在超净台中操作,超净台紫外灭菌30min后使用。在-80℃中取出甘油保存菌液,待菌液融化后使用。用无菌移液枪取上述制备的菌液100μL于装有4mLLB培养基的12mL摇菌管中,置于摇床中培养24小时。取上述制备菌液,使用LB培养基将菌液调至在酶联免疫检测仪OD600nm处测量值为0.10的菌液。然后,继续用LB培养基稀释2000倍后加入96孔板中(边缘用LB培养基填充)。以二甲基亚砜(DMSO)为溶剂,将25种甘草次酸-金配合物配置成5mmol母液冷冻储存。设置8个浓度梯度,终浓度分别为128,64,32,16,8,4,2和1μM,每个浓度设3个复孔,每孔加入0.4μL甘草次酸-金配合物溶液。将96孔板继续置于37℃培养箱中培养24小时,菌液完全澄清的最低单体化合物浓度可认为是最低抑菌浓度。
结果:化合物4-1-2、4-3和4-5体外抗CRAB活性较好,其最低抑菌浓度(MIC)值可以达到5μM,4-3的IC50(μM)为11.70±0.69(μM),4-5对LO2的IC50(μM)为12.54±2.10(μM),所以4-3,4-5对LO2毒性较大,而4-1-2对LO2与HepG2的IC50(μM)均大于20μM,所以4-1-2对LO2和HepG2的毒性较小,故选择4-1-2作为优势化合物(表5)。
表5 甘草次酸-金配合物对LO2和HepG2的IC50值及CRAB的MIC值
实施例4:甘草次酸-金配合物的基因毒性研究
为了确定甘草次酸-金化合物是否通过直接或间接损伤细胞DNA,产生抗菌作用。通过紫外吸收光谱法、荧光光谱法以及黏度测定来确定甘草次酸-金化合物是否具有基因毒性。
紫光吸收光谱法
用5mmolTris-HCI和50mmolNaCI配置成pH为7.4的Tris缓冲液。再称取适量的ct-DNA溶于一定的Tris缓冲溶液,滤液稀释至一定浓度,置入比色皿中,测量260nm和280nm的吸光度,测得ct-DNA溶液I260/I280=1.92(1.92>1.8),说明DNA基本不含蛋白质,不需进一步处理。然后,向ct-DNA溶液中加入4-1-2配置成药物浓度为0,0.01,0.02,0.04,0.08,0.16,0.32,0.64μM的混合溶液。最后,将混合溶液置于比色皿中,在190nm-325nm范围对混合溶液进行波长扫描。
结果:吸收峰随浓度增加而小幅度增加,但并未影响DNA分子在260nm处的吸收峰值。因此,4-1-2化合物对ct-DNA无作用。(图2)
荧光光谱法
首先配置含30μMEB和40μMct-DNA的Tris缓冲液,然后加入4-1-2配置成终浓度分别为0,10,20,30,40,50,60,70,80,90μM的混合溶液。将混合溶液置入荧光皿中,在F-2700型荧光光谱仪上设定激发光波长为518nm,记录525nm-725nm范围配合物的发射光谱。
结果:溶液的荧光强度随着DNA的加入变化微小,表明配合物4-1-2不能使溴化已腚从ct-DNA脱离出,配合物4-1-2与ct-DNA的作用微弱(图3)。
粘度测定
固定ct-DNA溶液的浓度为4.5mmol/L,置于乌氏粘度计并在SYP-Ⅱ型玻璃缸恒温水浴槽中恒温(25±0.1℃),恒温时间不少于10min。使用秒表记录ct-DNA溶液流经粘度计毛细管所需时间,重复测试3次,误差小于0.5s,取3次的平均值为t0。测试配合物对ct-DNA溶液粘度的影响时,逐次增加配合物的浓度,重复上述操作,记录ct-DNA和配合物的混合溶液流经粘度计毛细管所需时间,重复测试3次,误差小于0.5s,取平均值为t。按公式η=(t-t0)/t0计算相对粘度。(t0为缓冲溶液流经毛细管所需的时间,t为ct-DNA溶液流经毛细管所需的时间)。以(η/η0)对配合物浓度作图(η0为未与配合物混合的ct-DNA溶液的相对粘度)。
结果:随着药物浓度的增加,4-1-2的相对粘度与金诺芬相比更加稳定。说明4-1-2配合物与DNA作用较小(图4)。
综上所述,通过紫外吸收光谱法、荧光光谱法以及粘度的测定等,表明优势化合物4-1-2与ct-DNA作用微小,并非通过直接或间接损伤细胞DNA,产生的抗菌作用。
2个甘草次酸配体化合物结构式如表6所示:
表6所合成的配体化合物结构式
25个甘草次酸-金配合物结构式如表7所示:
表7所合成的甘草次酸-金配合物结构式
化合物4-1-2的氢谱
1H-NMR(500MHz,CDCl3)δ6.43–6.37(m,1H),6.13(dd,J=17.3,10.4Hz,1H),5.89(s,1H),5.83(d,J=11.4Hz,1H),4.97(d,J=15.4Hz,1H),4.65(d,J=15.5Hz,1H),4.61–4.56(m,3H),4.51–4.45(m,3H),4.29(s,6H),2.83(d,J=13.6Hz,1H),2.39(s,1H),2.18(d,J=10.7Hz,1H),2.06(dd,J=13.6,4.3Hz,1H),2.03(s,1H),2.00(s,1H),1.86(dd,J=13.6,4.1Hz,1H),1.82–1.76(m,1H),1.75(s,1H),1.71–1.69(m,1H),1.66(d,J=12.0Hz,2H),1.63–1.60(m,1H),1.50(d,J=12.2Hz,1H),1.45(s,1H),1.42(s,1H),1.39(s,1H),1.38(s,3H),1.33(d,J=3.3Hz,1H),1.31–1.27(m,1H),1.21(s,3H),1.17(s,3H),1.15(s,3H),1.13–1.08(m,1H),1.02(d,J=13.7Hz,1H),0.93(s,3H),0.91(d,J=6.1Hz,3H),0.86(s,1H),0.83(s,3H).
化合物4-3的氢谱
1H-NMR(500MHz,CDCl3)δ6.98–6.77(m,2H),5.89(s,1H),4.96(d,J=15.4Hz,1H),4.66(d,J=7.3Hz,1H),4.63(d,J=3.4Hz,1H),4.58(d,J=13.1Hz,3H),4.50(d,J=13.4Hz,3H),4.28(s,6H),3.81(d,J=17.9Hz,3H),2.85(d,J=13.8Hz,1H),2.39(s,1H),2.18(d,J=12.5Hz,1H),2.09–2.04(m,1H),2.01(s,1H),2.00(s,1H),1.88–1.81(m,1H),1.77(d,J=14.8Hz,1H),1.72(d,J=4.0Hz,1H),1.68(d,J=8.8Hz,1H),1.64(s,2H),1.61(d,J=8.6Hz,1H),1.50(d,J=12.2Hz,1H),1.45(s,1H),1.42(s,1H),1.38(s,3H),1.33(s,1H),1.30(s,1H),1.28(s,1H),1.21(s,3H),1.17(s,3H),1.15(s,3H),1.12–1.08(m,1H),1.02(d,J=13.0Hz,1H),0.94(s,3H),0.91(s,3H),0.89(d,J=7.1Hz,1H),0.87(d,J=8.1Hz,1H),0.83(s,3H).
化合物4-3的碳谱
13C-NMR(126MHz,CDCl3)δ200.02(s),175.82(s),169.37(s),165.56(s),164.68(s),134.44(s),132.85(s),128.48(s),81.94(s),77.24(s),73.26(d,J=7.5Hz),61.64(s),54.96(s),53.45(s),52.69–51.74(m),48.14(s),45.45(s),43.71(s),43.15(s),41.16(s),38.81(s),38.20(s),37.58(s),36.89(s),32.67(s),31.92(s),31.60(s),31.07(s),28.47(s),28.06(s),26.50(d,J=20.6Hz),26.33–25.88(m),23.37(d,J=15.6Hz),22.66(s),18.70(s),17.39(s),16.76(s),16.56(s),14.14(s)
化合物4-5的碳谱
13C-NMR(126MHz,CDCl3)δ200.09(s),175.82(s),169.31(s),166.01(s),130.19(s),129.09(s),128.50(s),80.70(s),77.24(s),73.25(d,J=7.5Hz),61.68(s),54.98(s),53.46(s),52.28(d,J=20.2Hz),52.11–51.92(m),48.14(s),45.46(s),43.72(s),43.14(s),41.16(s),38.55(d,J=81.4Hz),38.20–38.12(m),37.59(s),36.91(s),32.69(s),31.92(s),31.08(s),28.47(s),28.07(s),26.50(d,J=19.2Hz),23.51(s),23.30(s),18.70(s),17.40(s),16.77(s),16.58(s).
化合物4-5的氢谱
1H-NMR(500MHz,CDCl3)δ7.04–6.68(m,2H),5.89(s,1H),4.97(d,J=15.4Hz,1H),4.69–4.61(m,2H),4.58(d,J=13.1Hz,3H),4.50(d,J=13.5Hz,3H),4.28(s,6H),3.87–3.74(m,3H),2.84(t,J=11.9Hz,1H),2.39(s,1H),2.19(d,J=12.7Hz,1H),2.09–1.98(m,3H),1.84(dd,J=15.1,11.2Hz,1H),1.80–1.73(m,1H),1.73–1.69(m,1H),1.66(d,J=13.5Hz,1H),1.62(s,3H),1.50(d,J=12.6Hz,1H),1.45(s,1H),1.43(s,1H),1.38(s,3H),1.33(d,J=3.2Hz,1H),1.31–1.28(m,1H),1.21(d,J=7.8Hz,3H),1.17(s,3H),1.15(s,3H),1.13–1.07(m,1H),1.02(d,J=13.4Hz,1H),0.94(s,3H),0.91(s,3H),0.90–0.85(m,1H),0.83(s,3H).
化合物4-5的碳谱
13C-NMR(126MHz,CDCl3)δ200.02(s),175.82(s),169.38(s),165.56(s),164.68(s),134.44(s),132.85(s),128.48(s),81.94(s),77.24(s),73.25(d,J=7.5Hz),61.64(s),54.96(s),53.46(s),52.71–51.62(m),48.14(s),45.45(s),43.71(s),43.15(s),41.16(s),38.81(s),38.20(s),37.58(s),36.89(s),32.67(s),31.92(s),31.07(s),28.47(s),28.07(s),26.58(s),26.41(s),23.37(d,J=15.7Hz),18.70(s),17.39(s),16.75(s),16.56(s).
25个甘草次酸-金配合物结构式:
Claims (5)
1.一种甘草次酸-金配合物,其特征在于为18α,18β-甘草次酸和金(Ⅰ)膦的配合物。
3.根据权利要求1所述的甘草次酸-金配合物,其特征在于所述的R1选自H,R2选自PTA。
4.权利要求1-3中任一项所述的甘草次酸-金配合物在制备抗革兰氏阴性菌的药物中的应用。
5.权利要求1-3中任一项所述的甘草次酸-金配合物在制备抗耐碳青霉烯类鲍曼不动杆菌或制备耐碳青霉烯类鲍曼不动杆菌的药物中的应用。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101289467A (zh) * | 2008-06-12 | 2008-10-22 | 上海双科医药科技有限公司 | 有机酸铂盐及其制备方法和在制备抗癌药物中的应用 |
CN101775059A (zh) * | 2010-02-04 | 2010-07-14 | 中国药科大学 | 新的甘草次酸衍生物、其制备方法及其医药用途 |
CN105461781A (zh) * | 2015-12-17 | 2016-04-06 | 华南理工大学 | 一种茶皂苷元锌配合物及其制备方法和用途 |
CN107619425A (zh) * | 2017-09-21 | 2018-01-23 | 南京师范大学 | 一种尾接有机导向分子的芳基钌配合物及其合成方法和应用 |
CN113072611A (zh) * | 2021-04-06 | 2021-07-06 | 江西科技师范大学 | 一种甘草次酸修饰的多吡啶钌配合物及其制备方法和应用 |
CN113651868A (zh) * | 2021-09-22 | 2021-11-16 | 南京菲力康医药科技有限公司 | 基于顺铂衍生的含熊果酸配体的四价铂抗癌配合物及其制备方法和应用 |
-
2023
- 2023-03-20 CN CN202310268656.0A patent/CN116375788A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101289467A (zh) * | 2008-06-12 | 2008-10-22 | 上海双科医药科技有限公司 | 有机酸铂盐及其制备方法和在制备抗癌药物中的应用 |
CN101775059A (zh) * | 2010-02-04 | 2010-07-14 | 中国药科大学 | 新的甘草次酸衍生物、其制备方法及其医药用途 |
CN105461781A (zh) * | 2015-12-17 | 2016-04-06 | 华南理工大学 | 一种茶皂苷元锌配合物及其制备方法和用途 |
CN107619425A (zh) * | 2017-09-21 | 2018-01-23 | 南京师范大学 | 一种尾接有机导向分子的芳基钌配合物及其合成方法和应用 |
CN108929360A (zh) * | 2017-09-21 | 2018-12-04 | 南京师范大学 | 一类尾接有机导向分子的有机化合物及以该有机化合物为配体的芳基金属配合物 |
CN113072611A (zh) * | 2021-04-06 | 2021-07-06 | 江西科技师范大学 | 一种甘草次酸修饰的多吡啶钌配合物及其制备方法和应用 |
CN113651868A (zh) * | 2021-09-22 | 2021-11-16 | 南京菲力康医药科技有限公司 | 基于顺铂衍生的含熊果酸配体的四价铂抗癌配合物及其制备方法和应用 |
Non-Patent Citations (3)
Title |
---|
MIANLI BIAN等: "A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti-Ovarian-Cancer Agent by Inhibiting TrxR and Activating ROS-Mediated ERS", 《CHEMISTRY-A EUROPEAN JOURNAL》, 2 June 2020 (2020-06-02), pages 7094 * |
XIULI CHEN等: "Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase", 《REDOX BIOLOGY》, 1 February 2023 (2023-02-01), pages 1 - 16 * |
ZHIBIN YANG等: "Tumor-Targeting NHC−Au(I) Complex Induces Immunogenic Cell Death in Hepatocellular Carcinoma", 《JOURNAL OF MEDICINAL CHEMISTRY》, 24 February 2023 (2023-02-24), pages 3934 * |
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