Tang Sheng, Kong Lanying, Li Yinghong, Jiang Jiandong, Gao Limei, Cheng Xinyue, Ma Linlin, Zhang Xin, Li Yuhuan, Song Danqing
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China ; State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050, China.
ACS Med Chem Lett. 2015 Jan 7;6(2):183-6. doi: 10.1021/ml500525s. eCollection 2015 Feb 12.
Novel N-benzenesulfonyl sophocarpinic acid/ester and sophocarpinol derivatives were synthesized and evaluated for their antienteroviral activities against coxsackievirus type B3 (CVB3) from sophocarpine (1), a natural medicine isolated from Chinese herb. Structure-activity relationship (SAR) analysis revealed that the double bond and its geometrical configuration and position at the C-11 attachment did not greatly affect the potency. Among these derivatives, sophocarpinol 24d exerted the promising activities against not only CVB3 but also CVB1, CVB2, CVB5, and CVB6 with IC50 ranging from 0.62 to 3.63 μM (SI from 46 to 275), indicating a broad-spectrum antienteroviral characteristic. The SAR results provided the powerful information for further strategic optimization and development of a novel scaffold of broad-spectrum antiviral candidates against enteroviruses.
以从中药中分离得到的天然药物槐果碱（1）为原料，合成了新型N-苯磺酰基槐果酸/酯和槐果醇衍生物，并对其抗B3型柯萨奇病毒（CVB3）的抗肠道病毒活性进行了评价。构效关系（SAR）分析表明，C-11位连接的双键及其几何构型和位置对活性影响不大。在这些衍生物中，槐果醇24d不仅对CVB3有良好活性，对CVB1、CVB2、CVB5和CVB6也有活性，IC50范围为0.62至3.63 μM（SI为46至275），显示出广谱抗肠道病毒特性。SAR结果为进一步战略性优化和开发新型广谱抗肠道病毒候选药物支架提供了有力信息。
