摘要
利用药物设计的拼合原理,以黄体酮为原料,经过氧化开环、闭环、还原及缩合反应等步骤,设计合成了9个目标化合物,其结构经IR、NMR和HR-MS确证。以阿比特龙和5-氟脲嘧啶为阳性对照,采用MTT法初步评价目标化合物对体外人前列腺癌细胞PC-3、人卵巢癌细胞Skov3、人恶性黑色瘤细胞A375和人正常前列腺上皮细胞RWPE-1的抗增殖活性。结果显示,2-氨基-4-吡啶-4-基-6-(4′-氮杂孕甾-3′-酮-17′-基)烟腈、2-氨基-4-呋喃-2-基-6-(4′-氮杂孕甾-3′-酮-17′-基)烟腈对PC-3和Skov3细胞抗增殖活性优于阳性对照药阿比特龙和5-氟脲嘧啶。特别是2-氨基-4-吡啶-4-基-6-(4′-氮杂孕甾-3′-酮-17′-基)烟腈对PC-3细胞的IC50值为(2.73±0.80)μmol/L,明显优于阿比特龙,值得进一步研究。
Utilizing the principle of pharmacophore flattening, nine of new aza-steroidal pyridines derivatives have been synthesized by cleavage of A-ring, ring-closure, reduction and three-component reaction by progesterone as starting material, and their structures were confirmed by IR,NMR and HR-MS.The antitumor activity was evaluated against PC-3,Skov3,A375 and RWPE-1 cells in vitro by MTT assay, and abiraterone and 5-fluorouracil was used as a positive control.2-Amine-4-pyridinyl-6-(4′-aza-pregna-3′-one-17′-yl) nicotinonitrile and 2-amine-4-(fluran-2-yl)-6-(4′-aza-pregna-3′-one-17′-yl) nicotinonitrile had higher activity to inhibit PC-3 cells and Skov3 than abiraterone and 5-fluorouracil.The IC50 of 2-amine-4-pyridinyl-6-(4′-aza-pregna-3′-one-17′-yl) nicotinonitrile is(2.73±0.80) μmol/L,higher than abiraterone, is worthy of further study.
作者
左前进
蒋丽娟
吴爱群
ZUO Qian-jin;JIANG Li-juan;WU Aiqun(Hunan Kerui Bio-Pharmaceutical Co.,Ltd.,Shaoyang 422000,China;College of Chemistry and Chemical Engineering,Guangxi University for Nationalities,Nanning 530008,China;Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products,Guangxi Key Laboratory of Chemistry and Engineering of Forest Products,Key Laboratory of Chemistry and Engineering of Forest Products,State Ethnic Affairs Commission,Nanning 530006,China)
出处
《化学试剂》
CAS
北大核心
2021年第4期428-433,共6页
Chemical Reagents
基金
国家自然科学基金资助项目(21762006)。
关键词
氮杂甾体吡啶
合成
抗肿瘤活性
药物设计
aza-steroidal pyridines
synthesis
antitumor activity
drug design
