nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg searchdiv qikanlogo popupnotification paper
2022 04 v.44 514-521
青蒿素及其衍生物的抗寄生虫活性研究进展
基金项目(Foundation): 贵州省科技厅项目([2017]1219); 遵义市科技局项目(遵市科合社字(2018)27号,遵市科合支撑HZ字(2020)293号)
邮箱(Email): lei_chang@yeah.net;527822816@qq.com;
DOI: 10.13822/j.cnki.hxsj.2022008751
中文作者单位:

遵义医科大学药学院贵州省生物催化与手性药物合成重点实验室;

摘要(Abstract):

青蒿素是一种从菊科蒿属植物黄花蒿(Artemisia annua L.)中分离出来的倍半萜类天然产物,具有广泛的生物活性,如抗肿瘤、抗炎、抗菌、抗恶性疟原虫等。青蒿素也是重要的抗疟先导化合物,目前临床上使用的青蒿素类抗疟药物有双氢青蒿素、蒿甲醚、青蒿琥酯。近年来的研究发现,青蒿素及其衍生物对弓形虫、血吸虫、犬新孢子虫、利什曼原虫等多种病原体也具有广泛的抑制活性。主要综述近年来青蒿素及其衍生物抗虫活性研究进展,期望对新型抗寄生虫类青蒿素药物的研发有所帮助。

关键词(KeyWords): 青蒿素;结构修饰;衍生物;抗寄生虫;研究进展
参考文献

[1]GAO F,SUN Z,KONG F,et al.Artemisinin-derived hybrids and their anticancer activity[J].Eur.J.Med.Chem.,2020,188:112 044.

[2]ZYAD A,TILAOUI M,JAAFARI A,et al.More insights into the pharmacological effects of artemisinin[J].Phytother.Res.,2018,32(2):216-229.

[3]袁亚男,姜廷良,周兴,等.青蒿素的发现和发展[J].科学通报,2017,62(18):1 914-1 927.

[4]LOO C S N,LAM N S K,YU D,et al.Artemisinin and its derivatives in treating protozoan infections beyond malaria[J].Pharmacol.Res.,2017,117:192-217.

[5]李明,刘洪江,崔向军.青蒿素类药物在非疟疾疾病中的研究进展[J].中国全科医学,2018,21(12):1 508-1 512.

[6]张雪飞,王宏伟,韩少杰,等.青蒿素及其衍生物抗寄生虫研究进展[J].动物医学进展,2018,39(7):93-97.

[7]张婷,赵旭,桑晓宇,等.青蒿素及其衍生物抗寄生虫药理作用研究进展[J].动物医学进展,2017,38(10):98-102.

[8]王颖娜,张艳梅,蔺应学,等.恶性疟原虫对青蒿素类药物抗药性的最新研究进展[J].中国人兽共患病学报,2014,30(2):195-198.

[9]ROGERS W O,SEM R,TERO T,et al.Failure of artesunate-mefloquine combination therapy for uncomplicated plasmodium falciparum malaria in southern cambodia[J].Malar.J.,2009,8(1):1-9.

[10]BéRUBé G.An overview of molecular hybrids in drug discovery[J].Expert Opin.Drug Discov.,2016,11(3):281-305.

[11]TONY F,CHRISTOPH R,MOHAMED E M S,et al.Synthesis of thymoquinone-artemisinin hybrids:New potent antileukemia,antiviral and antimalarial agents[J].ACS Med.Chem.Lett.,2018,9(6):534-539.

[12]GUNJAN S,SHARMA T,YADAV K,et al.Artemisinin derivatives and synthetic trioxane trigger apoptotic cell death in asexual stages of plasmodium[J].Front.Cell.Infect.Microbiol.,2018,8:256.

[13]WANI W A,JAMEEL E,BAIG U,et al.Ferroquine and its derivatives:New generation of antimalarial agents[J].Eur.J.Med.Chem.,2015,101:534-551.

[14]REITER C,FR?HLICH T,ZEINO M,et al.New efficient artemisinin derived agents against human leukemia cells,human cytomegalovirus and Plasmodium falciparum:2nd generation 1,2,4-trioxane-ferrocene hybrids[J].Eur.J.Med.Chem.,2015,97:164-172.

[15]LANGE C D,COERTZEN D,SMIT F J,et al.Synthesis,in vitro antimalarial activities and cytotoxicities of amino-artemisinin-ferrocene derivatives[J].Bioorg.Med.Chem.Lett.,2018,28(3):289-292.

[16]LANGE C D,COERTZEN D,SMIT F J,et al.Synthesis,antimalarial activities and cytotoxicities of amino-artemisinin-1,2-disubstituted ferrocene hybrids[J].Bioorg.Med.Chem.Lett.,2018,28(19):3 161-3 163.

[17]?APCI A,HERRMANN L,SAMPATH KUMAR H M,et al.Artemisinin-derived dimers from a chemical perspective[J].Med.Res.Rev.,2021,41(6):2 927-2 970.

[18]CHATURVEDI D,GOSWAMI A,SAIKIA P P,et al.Artemisinin and its derivatives:A novel class of anti-malarial and anti-cancer agents[J].Chem.Soc.Rev.,2010,39(2):435-454.

[19]KARAG?Z A ?,REITER C,SEO E J,et al.Access to new highly potent antileukemia,antiviral and antimalarial agents via hybridization of natural products (homo)egonol,thymoquinone and artemisinin[J].Bioorg.Med.Chem.,2018,26(12):3 610-3 618.

[20]FR?HLICH T,HAHN F,BELMUDES L,et al.Synthesis of artemisinin-derived dimers,trimers and dendrimers:Investigation of their antimalarial and antiviral activities including putative mechanisms of action[J].Chem.Eur.J.,2018,24(32):8 103-8 113.

[21]TOROK D S,ZIFFER H.Synthesis and reactions of 11-azaartemisinin and derivatives[J].Tetrahedron Lett.,1995,36(6):829-832.

[22]HARMSE R,COERTZEN D,WONG H N,et al.Activities of 11-azaartemisinin and N-sulfonyl derivatives against asexual and transmissible malaria parasites[J].Chem.Med.Chem.,2017,12(24):2 086-2 093.

[23]SINGH C,VERMA V P,HASSAM M,et al.New orally active amino- and hydroxy-functionalized 11-azaartemisinins and their derivatives with high order of antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice[J].J.Med.Chem.,2014,57(6):2 489-2 497.

[24]THANH N L,WIM M D B,PHILIPPE G,et al.Synthesis of 11-aza-artemisinin derivatives using the Ugi reaction and an evaluation of their antimalarial activity[J].Tetrahedron Lett.,2014,55(35):4 892-4 894.

[25]BONEPALLY K R,HIRUMA T,MIZOGUCHI H,et al.Design and de novo synthesis of 6-aza-artemisinins[J].Org.Lett.,2018,20(15):4 667-4 671.

[26]BONEPALLY K R,TAKAHASHI N,MATSUOKA N,et al.Rapid and systematic exploration of chemical space relevant to artemisinins:Anti-malarial activities of skeletally diversified tetracyclic peroxides and 6-aza-artemisinins[J]J.Med.Chem.,2020,85(15):9 694-9 712.

[27]CRISTINA M D,DOU Z C,LUNGHI M,et al.Toxoplasma depends on lysosomal consumption of autophagosomes for persistent infection[J].Nat.Microbiol.,2017,2(8):17 096.

[28]VERCESI A E,RODRIGUES C O,UYEMURA S A,et al.Repiration and oxidative phosphorylation in the apicomplexan parasite Toxoplasma gondii[J].J.Biol.Chem.,1998,273(47):31 040-31 047.

[29]ZAWAWY L A E.Effect of artesunate on Toxoplasma gondii:In vitro and in vivo studies[J].J.Egypt.Soc.Parasitol.,2008,38(1):185-201.

[30]GOMES T C,ANDRADE ■,et al.In vitro action of antiparasitic drugs,especially artesunate,against Toxoplasma gondii[J].Rev.Soc.Bras.Med.Trop.,2012,45(4):485-490.

[31]ROSENBERG A,LUTH M R,WINZELER E A,et al.Evolution of resistance in vitro reveals mechanisms of artemisinin activity in Toxoplasma gondii[J].Proc.Natl.Acad.Sci.,2019,116(52):26 881-26 891.

[32]李婧美,金春美,管清香,等.3种青蒿素衍生物的抗疟原虫和弓形虫作用研究进展[J].延边大学医学学报,2019,42(1):73-76.

[33]JONES B L,D′ANGELO J,POSNER G H,et al.In vitro inhibition of Toxoplasma gondii by four new derivatives of artemisinin[J].Antimicrob.Agents Chemother.,2007,50(12):4 206-4 208.

[34]D′ANGELO J G,BORDON C,POSNER G H,et al.Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle[J].J.Antimicrob.Chemother.,2009,63(1):146-150.

[35]HEMPHILL A,MUELLER J,ESPOSITO M.Nitazoxanide,a broad spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections[J].Expert.Opin.Pharmacother.,2006,7(7):953-964.

[36]HENCKEN C P,JONES-BRANDO L,BORDON C,et al.Thiazole,oxadiazole,and carboxamide derivatives of artemisinin are highly selective and potent inhibitors of Toxoplasma gondii[J].J.Med.Chem.,2010,53(9):3 594-3 601.

[37]SCHULTZ T L,HENCKEN C P,WOODARD L E,et al.A thiazole derivative of artemisinin moderately reduces Toxoplasma gondii cyst burden in infected mice[J].J.Parasitol.,2014,100(4):516-521.

[38]DENG H,HUANG X,JIN C,et al.Synthesis,in vitro and in vivo biological evaluation of dihydroartemisinin derivatives with potential anti-Toxoplasma gondii agents[J].Bioorg.Chem.,2019,94:103 467.

[39]MCMANUS D P,BERGQUIST R,CAI P F,et al.Correction to:Schistosomiasis-from immunopathology to vaccines[C].Semin.Immunopathol.,2020,42(3):373-374.

[40]BOTROS S,SAYED H,AMER N,et al.Current status of sensitivity to praziquantel in a focus of potential drug resistance in Egypt[J].Int.J.Parasitol.,2005,35(7):787-791.

[41]LI H J,XU F L,WANG Y H,et al.Dihydroartemisinin:A new story of an old drug against Schistosoma mansoni infection[J].Parasitol.Res.,2014,113(1):239-241.

[42]GOLD D,ALIAN M,DOMB A,et al.Elimination of Schistosoma mansoni in infected mice by slow release of artemisone[J].Int.J.Parasitol.Drugs Drug Resist.,2017,7(2):241-247.

[43]KEISER J,N′GUESSAN N A,ADOUBRYN K D,et al.Efficacy and safety of mefloquine,artesunate,mefloquine-artesunate,and praziquantel against Schistosoma haematobium:Randomized,exploratory open-label trial[J].Clin.Infect.Dis.,2010,50(9):1 205-1 213.

[44]DUAN W W,QIU S J,ZHAO Y,et al.Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum[J].Bioorg.Med.Chem.Lett.,2012,22(4):1 587-1 590.

[45]WANG X L,YU D,LI C X,et al.In vitro and in vivo activities of DW-3-15,a commercial praziquantel derivative,against Schistosoma japonicum[J].Parasite.Vector.,2019,12(1):1-13.

[46]CORRêA S D A P,OLIVEIRA R N D,MENDES T M F,et al.In vitro and in vivo evaluation of six artemisinin derivatives against Schistosoma mansoni[J].Parasitol.Res.,2019,118(2):505-516.

[47]ALVAR J,VéLEZ I D,BERN C,et al.Leishmaniasis world wide and global estimates of its incidence[J].Plos One,2012,7(5):e35 671.

[48]MOREIRA V R,DE JESUS L C L,SOARES R E P,et al.Meglumine antimoniate (glucantime) causes oxidative stress-derived DNA damage in BALB/c mice infected by leishmania (leishmania) infantum[J].Antimicrob.Agents Chemother.,2017,61(6):2 360-2 316.

[49]EBRAHIMISADR P,GHAFFARIFAR F,HASSAN Z.In vitro evaluation of antileishmanial activity and toxicity of artemether with focus on its apoptotic effect[J].Iran.J.Pharm.Res.,2013,12(4):903-909.

[50]GHAFFARIFAR F,HEYDARI F,DALIMI A,et al.Evaluation of apoptotic and Antileishmanial activities of artemisinin on promastigotes and BALB/c mice infected with Leishmania major,Iran[J].Iran.J.Parasitol.,2015,10(2):258-267.

[51]PONTE-SUCRE A,GAMARRO F,DUJARDIN J C,et al.Drug resistance and treatment failure in leishmaniasis:A 21st century challenge[J].Plos Negl.Trop.D.,2017,11(12):e0 006 052.

[52]AVERY M A,MURALEEDHARAN K M,DESAI P V,et al.Structure-activity relationships of the antimalarial agent artemisinin.8.Design,synthesis,and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria[J].J.Med.Chem.,2003,46(20):4 244-4 258.

[53]MENON R,KANNOTH M,TEKWANI B,et al.A new library of C-16 modified artemisinin analogs and evaluation of their anti-parasitic activities[J].Comb.Chem.High Throughput Screen.,2006,9(10):729-741.

[54]CHOLLET C,CROUSSE B,BORIES C,et al.In vitro antileishmanial activity of fluoro-artemisinin derivatives against Leishmania donovani[J].Biomed.Pharmacother.,2008,62(7):462-465.

[55]AUCAMP J,ZUMA N H,N′DA D D.In vitro efficacy of synthesized artemisinin derivatives against Leishmania promastigotes[J].Bioorg.Med.Chem.Lett.,2020,30(22):127 581.

[56]BRUN R,BLUM J,CHAPPUIS F,et al.Human african trypanosomiasis[J].Lancet,2010,375(9 709):148-159.

[57]JOLAYEMI K,MAMMAN M,SANI D,et al.In vitro and in vivo changes observed in Trypanosoma brucei brucei-infected rats treated with artesunate and/or diminazene aceturate[J].Sokoto J.Vet.Sci.,2020,18(4):211-220.

[58]JOLAYEMI K O,MAMMAN M,SANI D,et al.In vitro assay and in vivo effect of artemisinin in Trypanosoma brucei brucei-infected wistar rats[J].Phytomedicine Plus,2021,1(3):100 061.

[59]MISHINA Y V,KRISHNA S,HAYNES R K,et al.Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth[J].Antimicrob.Agents Chemother.,2007,51(5):1 852-1 854.

[60]KIM J T,PARK J Y,SEO H S,et al.In vitro antiprotozoal effects of artemisinin on Neospora caninum[J].Vet.Parasitol.,2002,103(1/2):53-63.

[61]MAZUZ M L,HAYNES R,SHKAP V,et al.Neospora caninum:In vivo and in vitro treatment with artemisone[J].Vet.Parasitol.,2012,187(1/2):99-104.

[62]JOACHIM M,VRENI B,PABLO W,et al.In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts[J].Int.J.Antimicrob.Agents,2015,46(1):88-93.

[63]HARMSE R,WONG H N,SMIT F J,et al.Activities of 11-azaartemisinin and n-sulfonyl derivatives against Neospora caninum and comparative cytotoxicities[J].ChemMedChem,2017,12(24):2 094-2 098.

基本信息:

DOI:10.13822/j.cnki.hxsj.2022008751

中图分类号:R285

引用信息:

[1]翟荣航,王合珍,王京等.青蒿素及其衍生物的抗寄生虫活性研究进展[J].化学试剂,2022,44(04):514-521.DOI:10.13822/j.cnki.hxsj.2022008751.

基金信息:

贵州省科技厅项目([2017]1219); 遵义市科技局项目(遵市科合社字(2018)27号,遵市科合支撑HZ字(2020)293号)

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文