沈阳药科大学学报

年中国药科大学获批国家自然科学基金资助项目 

来源:沈阳药科大学学报 【在线投稿】 栏目:期刊导读 时间:2021-04-25
中圃粟种太.誊学报Journal ofChinⅡPhomⅡceMf;c。f洳觇瑙毋第43卷3结果与讨论初步实验结果表明,呋咱氮氧化物类BA.NO衍生物对两种肿瘤细胞显示较强的抑制活性。其中,化合物14a和149抗肝癌细胞活性最强,高、中、低3种浓度下均强于母体药物BA,1×10。5 moL/L浓度下作用与紫杉醇相当;所有呋咱氮氧化物类BA衍生物(14a~149)在中、低浓度下对鼠黑色素瘤B16细胞的抑制作用均强于BA。而硝酸酯类衍生物除化合物12a有较弱活性外,其余3个均无细胞毒性。初步构效关系分析可知,对于BA的28一COOH呋咱氮氧化物杂合物,连接基团对抗肝癌细胞活性有一定的影响:1)随碳链长度增长,活性呈下降的趋势(14a>14b>14c>14d);2)连接基团中含有0杂原子能增强化合物的细胞毒性(149);此类化合物对鼠黑色素瘤B16细胞的抑制作用未呈现明显的构效关系,化合物14c及14f表现出相对更强的活性。相比于呋咱氮氧化物类NO供体型衍生物,硝酸酯类衍生物未显示出对肿瘤细胞的细胞毒性,这与之前报道的部分70A一硝酸酯杂合物研究结果基本一致,可能是由于硝酸酯释放的NO浓度较低,而低浓度的NO有促进细胞生长的作用,却无细胞毒性作用。’本文所得的初步活性数据表明,多数呋咱氮氧HepG2细胞及鼠黑色素瘤B16细胞显示较强的抑制作用,有待进一步深入研究。参考文献[1]FuldaS.Betulinic acid for cancer treatment and prevention[J].IntJMofSci,2008,9(6):i096—1107.[2]SteeleJCP,WarhurstDC,KirbyGC,et a1.In vitro and in vivo evaluation of betulinic acid as an antimalarial『J].PhytotheraRes,1999,13(2):115—119.[3]SelzerE,EmilioP,VolkerW,et a1.Effects of betulinic acid alone and in combination with irradiation in human melanoma 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