Evaluation of artemisinin derivative artemether as a fluconazole potentiator through inhibition of Pdr5.
Evaluation of artemisinin derivative artemether as a fluconazole potentiator through inhibition of Pdr5.
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通过抑制 Pdr5 评价青蒿素衍生物蒿甲醚作为氟康唑增效剂的作用。
DOI：
10.1016/j.bmc.2021.116293
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发表时间：
2021-06
影响因子：
3.5
通讯作者：
Wang Hui
中科院分区：
文献类型：
--
作者：
Zhou Jia;Li Jinyang;Cheong Iohong;Liu Ning-Ning;Wang Hui
抗真菌药物由于其有限的使用条件和耐药性而越来越受到人们的关注。药物再利用在发现抗真菌药物方面具有很大的潜力。本研究探讨了青蒿素及其衍生物双氢青蒿素、青蒿琥酯和蒿甲醚的抗真菌活性。我们发现青蒿素可以抑制白色念珠菌的生长，并可以增强三种常用抗真菌药物两性霉素B、米卡芬金和氟康唑（FLC）的活性，对白色念珠菌的生长和丝化具有抑制作用。青蒿素与FLC具有较强的抗真菌作用。在青蒿素中，蒿甲醚对FLC的抗真菌活性最强，可使FLC耐药临床分离株恢复对FLC的敏感性。蒿甲醚与FLC的联合抑菌作用是广谱的，可以抑制耳念珠菌、热带念珠菌、假丝酵母菌、酿酒酵母菌和新生隐球菌的生长。机制研究表明，蒿甲醚可能通过破坏Pdr5的功能，导致FLC在细胞内积聚，从而增强唑的疗效。本研究发现蒿甲醚是一种新的FLC增强剂，为抗真菌感染和抗真菌耐药性提供了潜在的治疗见解。
Antifungal development has gained increasing attention due to its limited armamentarium and drug resistance. Drug repurposing holds great potential in antifungal discovery. In this study, we explored the antifungal activity of artemisinin and its derivatives, dihydroartemisinin, artesunate and artemether. We identified that artemisinins can inhibit the growth ofCandida albicans, and can enhance the activity of three commonly used antifungals, amphotericin B, micafungin and fluconazole (FLC), onCandida albicansgrowth and filamentation. Artemisinins possess stronger antifungal effect with FLC than with other antifungals. Among artemisinins, artemether exhibits the most potent antifungal activity with FLC and can recover the susceptibility of FLC-resistant clinical isolates to FLC treatment. The combinatorial antifungal activity of artemether and FLC is broad-spectrum, as it can inhibit the growth ofCandida auris,Candida tropicalis,Candida parapsilosis,Saccharomyces cerevisiaeandCryptococcus neoformans. Mechanistic investigation revealed that artemether might enhance azole efficacy through disrupting the function of Pdr5, leading to intracellular accumulation of FLC. This study identified artemether as a novel FLC potentiator, providing potential therapeutic insights against fungal infection and antifungal resistance.
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DOI：
10.1007/s40278-017-38968-3
发表时间：
2017
期刊：
Reactions Weekly
影响因子：
--
作者：
S. Campoy;J. L. Adrio
通讯作者：
S. Campoy;J. L. Adrio
DOI：
10.1016/s0140-6736(20)30552-3
发表时间：
2020-04-25
期刊：
Lancet (London, England)
影响因子：
--
作者：
van der Pluijm RW;Tripura R;Hoglund RM;Pyae Phyo A;Lek D;Ul Islam A;Anvikar AR;Satpathi P;Satpathi S;Behera PK;Tripura A;Baidya S;Onyamboko M;Chau NH;Sovann Y;Suon S;Sreng S;Mao S;Oun S;Yen S;Amaratunga C;Chutasmit K;Saelow C;Runcharern R;Kaewmok W;Hoa NT;Thanh NV;Hanboonkunupakarn B;Callery JJ;Mohanty AK;Heaton J;Thant M;Gantait K;Ghosh T;Amato R;Pearson RD;Jacob CG;Gonçalves S;Mukaka M;Waithira N;Woodrow CJ;Grobusch MP;van Vugt M;Fairhurst RM;Cheah PY;Peto TJ;von Seidlein L;Dhorda M;Maude RJ;Winterberg M;Thuy-Nhien NT;Kwiatkowski DP;Imwong M;Jittamala P;Lin K;Hlaing TM;Chotivanich K;Huy R;Fanello C;Ashley E;Mayxay M;Newton PN;Hien TT;Valecha N;Smithuis F;Pukrittayakamee S;Faiz A;Miotto O;Tarning J;Day NPJ;White NJ;Dondorp AM;Tracking Resistance to Artemisinin Collaboration
通讯作者：
Tracking Resistance to Artemisinin Collaboration
DOI：
10.1016/j.jchromb.2007.01.012
发表时间：
2007-06
期刊：
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
影响因子：
--
作者：
Sung-Su Kim;Ho-Taek Im;I. Kang;Hyun-Su Lee;Heon‐Woo Lee;Sung-Hee Cho;Jong-Bin Kim;Kyung-Tae Lee-Kyung
通讯作者：
Sung-Su Kim;Ho-Taek Im;I. Kang;Hyun-Su Lee;Heon‐Woo Lee;Sung-Hee Cho;Jong-Bin Kim;Kyung-Tae Lee-Kyung
影响因子：
2.8
作者：
Eschenauer, Gregory;Depestel, Daryl D;Carver, Peggy L
通讯作者：
Carver, Peggy L
影响因子：
4.8
作者：
Kolaczkowski, M;vanderRest, M;Goffeau, A
通讯作者：
Goffeau, A