{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:11:54Z","timestamp":1789434714770,"version":"build-2803163510"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We reported recently that the bloodstream form of the African trypanosome,<jats:italic>Trypanosoma brucei<\/jats:italic>, is sensitive to the anti-influenza virus drug rimantadine. In the present report we describe the trypanocidal properties of a further 62 aminoadamantane and aminoalkylcyclohexane derivatives. Seventeen of the compounds were found to be more active than rimantadine, with four inhibiting growth in vitro of<jats:italic>T. brucei<\/jats:italic>by &gt;90% at concentrations of 1 \u03bcM. The most active derivative (1-adamantyl-4-amino-cyclohexane) was about 20 to 25 times more effective than rimantadine. We observed a correlation between structural features of the derivatives and their trypanocidal properties; hydrophobic substitutions to the adamantane or cyclohexane rings generally enhanced activity. As with rimantadine, the activity in vitro varied with the pH.<jats:italic>T. brucei<\/jats:italic>was more sensitive in an alkaline environment (including a normal bloodstream pH of 7.4) and less sensitive under acidic conditions. Tests for activity in vivo were carried out with a mouse model of infection with a virulent strain of<jats:italic>T. brucei<\/jats:italic>. Although the parasitemia was not eliminated, it could be transiently suppressed by &gt;98% with the most active compounds tested. These results suggest that aminoadamantane derivatives could have potential as a new class of trypanocidal agents.<\/jats:p>","DOI":"10.1128\/aac.45.5.1360-1366.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:56:57Z","timestamp":1027763817000},"page":"1360-1366","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["In Vitro and In Vivo Activities of Aminoadamantane and Aminoalkylcyclohexane Derivatives against<i>Trypanosoma brucei<\/i>"],"prefix":"10.1128","volume":"45","author":[{"given":"John M.","family":"Kelly","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guenter","family":"Quack","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Merz and Co., D-60318 Frankfurt, Germany2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Miles","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.7.1140"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.11.2228"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/S0140-6736(98)00416-4","article-title":"The fall and rise of sleeping sickness.","volume":"353","author":"Barrett M. P.","year":"1999","unstructured":"Barrett M. P. The fall and rise of sleeping sickness. Lancet 353 1999 1113 1114","journal-title":"Lancet"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1093\/infdis\/159.6.1050","article-title":"Biological potential for amantadine-resistant influenza A virus in an avian model.","volume":"159","author":"Bean W. J.","year":"1989","unstructured":"Bean W. J. Threlkheld S. C. Webster R. G. Biological potential for amantadine-resistant influenza A virus in an avian model. J. Infect. Dis. 159 1989 1050 1056","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1113\/jphysiol.1996.sp021495","article-title":"Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells.","volume":"494","author":"Chizhmakov I. V.","year":"1996","unstructured":"Chizhmakov I. V. Geraghty F. M. Ogden D. C. Hayhurst A. Antoniou M. Hay A. J. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. J. Physiol. 494 1996 329 336","journal-title":"J. Physiol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1097\/00001432-199712000-00011","article-title":"Chemotherapy for leishmaniasis and trypanosomiasis.","volume":"10","author":"Gompel A. V.","year":"1997","unstructured":"Gompel A. V. Vervoort T. Chemotherapy for leishmaniasis and trypanosomiasis. Curr. Opin. Infect. Dis. 10 1997 469 474","journal-title":"Curr. Opin. Infect. Dis."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb04038.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.2.226"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.28.2.216"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2307\/3282883"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.11.1699"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.4.985"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0006-8993(94)90821-4","article-title":"Amantadine increases the extracellular dopamine levels in the striatum by re-uptake inhibition and by N-methyl-d-aspartate receptor antagonism.","volume":"662","author":"Mizoguchi K.","year":"1994","unstructured":"Mizoguchi K. Yokoo H. Yoshida M. Tanaka T. Tanaka M. Amantadine increases the extracellular dopamine levels in the striatum by re-uptake inhibition and by N-methyl-d-aspartate receptor antagonism. Brain Res. 662 1994 255 258","journal-title":"Brain Res."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.26.1.101"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-308X(08)60410-8","article-title":"The treatment of human African trypanosomiasis.","volume":"33","author":"Pepin J.","year":"1994","unstructured":"Pepin J. Milford F. The treatment of human African trypanosomiasis. Adv. Parasitol. 33 1994 1 47","journal-title":"Adv. Parasitol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0966-842X(00)88942-8","article-title":"Understanding the mechanism of action of the anti-influenza virus drug amantadine.","volume":"3","author":"Pinto L. H.","year":"1992","unstructured":"Pinto L. H. Lamb R. A. Understanding the mechanism of action of the anti-influenza virus drug amantadine. Trends Microbiol. 3 1992 271","journal-title":"Trends Microbiol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90452-I"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"888","DOI":"10.2460\/ajvr.1999.60.07.888","article-title":"Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza A2.","volume":"60","author":"Rees W. A.","year":"1999","unstructured":"Rees W. A. Harkins J. D. Lu M. Holland R. E. Jr. Lehner A. F. Tobin T. Chambers T. M. Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza A2. Am. J. Vet. Res. 60 1999 888 894","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0966-842X(97)01200-6","article-title":"Changing the end: variation orchestrated at the telomeres of African trypanosomes.","volume":"6","author":"Rudenko G.","year":"1998","unstructured":"Rudenko G. Cross G. A. M. Borst P. Changing the end: variation orchestrated at the telomeres of African trypanosomes. Trends Microbiol. 6 1998 113 116","journal-title":"Trends Microbiol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S1369-5274(99)00039-9","article-title":"Genes involved in phenotypic and antigenic variation in African trypanosomes and malaria.","volume":"2","author":"Rudenko G.","year":"1999","unstructured":"Rudenko G. Genes involved in phenotypic and antigenic variation in African trypanosomes and malaria. Curr. Opin. Microbiol. 2 1999 651 656","journal-title":"Curr. Opin. Microbiol."},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0166-3542(97)00061-2","article-title":"How to overcome resistance to influenza A viruses against adamantane derivatives.","volume":"37","author":"Scholtissek C.","year":"1998","unstructured":"Scholtissek C. Quack G. Klenk H. D. Webster R. G. How to overcome resistance to influenza A viruses against adamantane derivatives. Antivir. Res. 37 1998 83 95","journal-title":"Antivir. Res."},{"key":"e_1_3_2_23_2","first-page":"516","article-title":"Transport of amantadine and rimantadine through the blood-brain barrier.","volume":"244","author":"Spector R.","year":"1988","unstructured":"Spector R. Transport of amantadine and rimantadine through the blood-brain barrier. J. Pharmacol. Exp. Res. 244 1988 516 519","journal-title":"J. Pharmacol. Exp. Res."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"11525","DOI":"10.1073\/pnas.88.24.11525","article-title":"Amantadine selection of a mutant influenza virus containing an acid-stable haemagglutinin glycoprotein: evidence for virus-specific regulation of the pH of glycoprotein transport vesicles.","volume":"88","author":"Steinhauer D. A.","year":"1991","unstructured":"Steinhauer D. A. Wharton S. W. Skehel J. J. Wiley D. C. Hay A. J. Amantadine selection of a mutant influenza virus containing an acid-stable haemagglutinin glycoprotein: evidence for virus-specific regulation of the pH of glycoprotein transport vesicles. Proc. Natl. Acad. Sci. USA 88 1991 11525 11529","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1083\/jcb.139.1.103","article-title":"The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice.","volume":"139","author":"Webb H.","year":"1997","unstructured":"Webb H. Carnall N. Vanhamme L. Rolin S. Van Den Abbeele J. Welburn S. Pays E. Carrington M. The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice. J. Cell Biol. 139 1997 103 114","journal-title":"J. Cell Biol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0169-4758(99)01490-8","article-title":"Sleeping sickness rediscovered.","volume":"15","author":"Welburn S. C.","year":"1999","unstructured":"Welburn S. C. Fevre E. Coleman P. Sleeping sickness rediscovered. Parasitol. Today. 15 1999 303 305","journal-title":"Parasitol. Today."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.5.826"},{"key":"e_1_3_2_28_2","unstructured":"World Health Organisation Control of tropical diseases: sleeping sickness. 1994 World Health Organization Geneva Switzerland"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.45.5.1360-1366.2001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.45.5.1360-1366.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T19:51:46Z","timestamp":1733687506000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.45.5.1360-1366.2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,5]]}},"alternative-id":["10.1128\/AAC.45.5.1360-1366.2001"],"URL":"https:\/\/doi.org\/10.1128\/aac.45.5.1360-1366.2001","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5]]},"assertion":[{"value":"2000-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}