{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:32:27Z","timestamp":1760851947854},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,12,21]],"date-time":"2001-12-21T00:00:00Z","timestamp":1008892800000},"content-version":"vor","delay-in-days":234,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:p>About 160 fluoroquinolones and derivatives were tested for antitrypanosomal activity in a drug sensitivity assay followed by fluorometric evaluation. The most active quinolone compounds had IC<jats:sub>50<\/jats:sub> values in the range from 100 to 900\u2003ng\/ml, while several derivatives were not active at a concentration of 100\u2003\u03bcg\/ml. In a structure activity relationship study, modification of the quinolones at position R1, R2, R3 and R8 did not influence trypanocidal activity. An exchange of the fluor at position 6 may contribute to an increase in activity but does not entirely control it. Pyrrolidine substituents at position R7 generally were more active than other substituents at this position. Tetracyclic quinolone derivatives were amongst the most active compounds with IC<jats:sub>50<\/jats:sub> values in the range of 0.3\u20138.8\u2003\u03bcg\/ml. The <jats:italic>in vitro<\/jats:italic> cytotoxicity on HT\u201029 cells was determined for active compounds with IC<jats:sub>50<\/jats:sub> values below 1\u2003\u03bcg\/ml. In addition, six drugs with an IC<jats:sub>50<\/jats:sub> below 1\u2003\u03bcg\/ml and a selectivity index of more than 10 were chosen for <jats:italic>in vivo<\/jats:italic> experiments. Dose escalation experiments with a maximum dose of 100\u2003mg\/kg\/bid were performed in a mouse model without central nervous system involvement. For unknown reasons the <jats:italic>in vitro<\/jats:italic> effect of the drugs could not be confirmed <jats:italic>in vivo<\/jats:italic>, but the class of compound remains of interest for their mode of action, the low toxicity, pharmacological properties and the availability of a large number of synthesized compounds.<\/jats:p>","DOI":"10.1046\/j.1365-3156.2001.00713.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T21:37:30Z","timestamp":1047505050000},"page":"369-389","source":"Crossref","is-referenced-by-count":20,"title":["Evaluation of quinolone derivatives for antitrypanosomal activity"],"prefix":"10.1111","volume":"6","author":[{"given":"J.","family":"Keiser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Burri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb03772.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.55.070186.003413"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000007146"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(88)90017-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/33.4.685"},{"key":"e_1_2_6_7_2","first-page":"407","article-title":"Synthesis and activity of some quinolone derivatives against Plasmodium falciparum in vitro","volume":"51","author":"Dominguez J","year":"1996","journal-title":"Il Farmaco"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.51.070182.003403"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1949.s1-29.173"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)02156-6"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706X(93)90083-N"},{"key":"e_1_2_6_12_2","first-page":"315","article-title":"An \u201cin vitro selectivity index\u201d for evaluation of cytotoxicity of antitrypanosomal compounds","volume":"9","author":"Kaminsky R","year":"1996","journal-title":"In Vitro Toxicity"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60526-4"},{"key":"e_1_2_6_14_2","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1128\/AAC.43.8.2066","article-title":"Antitrypanosomal activity of fluoroquinolones","volume":"43","author":"Nenortas E","year":"1999","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/26.suppl_B.1"},{"key":"e_1_2_6_16_2","first-page":"473","article-title":"A new fluorometric assays for cytotoxicity measurements in vitro","volume":"3","author":"Pag\u00e9 B","year":"1993","journal-title":"International Journal of Oncology"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(94)90430-8"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00931138"},{"key":"e_1_2_6_19_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0001-706X(97)00079-X","article-title":"The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T. b. rhodesiense and T. b. gambiense) in vitro","volume":"68","author":"R\u00e4z B","year":"1997","journal-title":"Acta Tropica"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.Supplement_5.S1194"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a011692"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287399509531978"},{"key":"e_1_2_6_23_2","unstructured":"Van NieuwenhoveS(1998)Current sleeping sickness situation and control strategies. 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