大观霉素磺酰化衍生物的合成及抗微生物活性研究  

Synthesis and antimicrobial activity of sulfonamide derivatives of spectinomycin

作　　者：李永清 范莉 王巍[2] 朱洪林 韦俊宏[2] 杨大成 LI Yong-qing;FAN Li;WANG Wei;ZHU Hong-lin;WEI Jun-hong;YANG Da-cheng(Key Laboratory of Applied Chemistry of Chongqing Municipality,School of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715,China;State Key Laboratory of Resource Insects,Southwest University,Chongqing 400715,China)

机构地区：[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]西南大学,资源昆虫高效养殖与利用全国重点实验室,重庆400715

出　　处：《药学学报》2024年第5期1313-1326,共14页Acta Pharmaceutica Sinica

基　　金：资源昆虫高效养殖与利用全国重点实验室开放课题(SKLSGB-ORP202203);中央高校基本科研业务费专项资金(SWU-KR22009)。

摘　　要：微孢子虫是一类威胁畜牧渔生产与人类健康的胞内寄生真核微生物,但目前尚无专用微孢子虫化学治疗药物。基于大观霉素的低毒性和磺酰胺的良好药学性质,作者设计了大观霉素的磺酰胺类衍生物;通过反应条件探索,以52%~74%的收率合成了21个目标分子,并通过氢谱、碳谱、高分辨质谱等确证了分子结构;通过体外筛选,研究了目标分子的宿主细胞毒性和对脊椎动物微孢子虫代表-海伦脑炎微孢子虫的生物活性,发现各有4个目标分子能抑制或促进海伦脑炎微孢子虫增殖。本研究建立了大观霉素的磺酰胺类衍生物的合成方法,发现了对海伦脑炎微孢子虫有效的新型化合物,为大观霉素的进一步衍生及微孢子虫治疗药物的发现提供了新的思路。Microsporidia is a group of intracellular parasitic eukaryotic microorganisms that pose threats to livestock fish production and human health,but there is no special chemo-therapeutic drug available for the treatment of microsporidia currently.In this study,sulfonamide derivatives of spectinomycin were designed by taking into consideration the low toxicity of spectinomycin and the favorable pharmaceutical properties of sulfonamides.Through the exploration of reaction conditions,a total of 21 target molecules were synthesized with a yield of 52%-74%and their chemical structures were confirmed by 1H NMR,13C NMR,and high resolution mass spectrometry(HR MS).By screening in vitro,the host cell cytotoxicity and biological activity of target molecules to Encephalitozoon hellem,a representative of vertebrates infecting microsporidia,were studied.It was found that four target molecules each could inhibit or promote the proliferation of E.hellem.In this study,the synthesis method of sulfonamide derivatives of spectinomycin was established,and new compounds effective against E.hellem were discovered,which provided a new idea for the further derivatization of spectinomycin and the development of therapeutic drugs targeting microsporidia.

关 键 词：大观霉素 磺酰氯 磺酰胺 海伦脑炎微孢子虫 生物活性 

分 类 号：R284[医药卫生—中药学]