药学学报, 2022, 57(5): 1429-1439
引用本文:
李文粒, 范莉, 刘寒驰, 彭诗琦, 李鑫, 郑怡, 吴景灏, 李芬芬, 杨大成. 含有四氮唑砜基的辛弗林磺酰胺衍生物的合成及其抗菌活性研究[J]. 药学学报, 2022, 57(5): 1429-1439.
LI Wen-li, FAN Li, LIU Han-chi, PENG Shi-qi, LI Xin, ZHENG Yi, WU Jing-hao, LI Fen-fen, YANG Da-cheng. Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups[J]. Acta Pharmaceutica Sinica, 2022, 57(5): 1429-1439.

含有四氮唑砜基的辛弗林磺酰胺衍生物的合成及其抗菌活性研究
李文粒1, 范莉1*, 刘寒驰1, 彭诗琦2, 李鑫2, 郑怡1, 吴景灏1, 李芬芬1, 杨大成1*
1. 西南大学化学化工学院, 重庆市高校应用化学重点实验室, 重庆 400715;
2. 重庆市第八中学校, 重庆 400030
摘要:
辛弗林是存在于枳实中的天然小分子生物碱,具有多种生物活性,但其衍生物研究较少。基于多靶点药物设计策略,采用分子拼接法,对辛弗林酚羟基和仲胺基进行结构修饰,设计并合成了5个中间体和15个目标分子,所得化合物测试了抗人致病菌和抗真菌活性,发现2个中间体IM4IM5抗大肠杆菌活性和阳性对照8种氟喹诺酮药物相当;TM1n对耐药热带假丝酵母菌和耐药白色念珠菌抑制活性强于氟康唑,TM1dTM1f对白色念珠菌ATCC90023、TM1oTM1f对耐药白色念珠菌以及TM1f对近平滑念珠菌ATCC2019的抑制活性均和氟康唑相当,都具有深入研究的潜力。本研究首次发现了对人致病真菌具有高抑制活性的辛弗林衍生物,为辛弗林的进一步研究提供了新的思路。
关键词:    辛弗林      1-甲基-5-巯基-1H-四氮唑            磺酰胺      抗人致病菌活性      抗真菌活性     
Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups
LI Wen-li1, FAN Li1*, LIU Han-chi1, PENG Shi-qi2, LI Xin2, ZHENG Yi1, WU Jing-hao1, LI Fen-fen1, YANG Da-cheng1*
1. Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China;
2. Chongqing No. 8 Secondary School, Chongqing 400030, China
Abstract:
Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole.TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.
Key words:    synephrine    1-methyl-5-mercapto-1H-tetrazole    sulfone    sulfonamide    activity against human pathogenic bacteria    activity against human pathogenic fungal   
收稿日期: 2022-01-14
DOI: 10.16438/j.0513-4870.2022-0059
基金项目: 重庆市技术创新与应用发展专项面上项目(cstc2019jscx-msxmX0123);重庆市雏鹰计划研究项目(CY210234);重庆市大学生创新创业训练计划项目(S202010635028).
通讯作者: 杨大成,Tel:13640566978,E-mail:hxydc@swu.edu.cn;范莉,Tel:13594205818,E-mail:hxfanl@swu.edu.cn
Email: hxydc@swu.edu.cn;hxfanl@swu.edu.cn
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