{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:45:54Z","timestamp":1790973954173,"version":"4.1.0"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"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":[[2000,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Twelve new dithiaarsanes were evaluated for their in vitro and in vivo trypanocidal properties in regard to their three parent molecules, 4-amino-phenylarsenoxide, melarsenoxide, and 4-dansylamino-phenylarsenoxide. The most potent dithiaarsane, compound 2b, had a minimum effective concentration of 1.5 nM after 48 h of incubation and at a dose of 0.39 \u03bcmol\/kg of body weight (0.2 mg\/kg) administered subcutaneously cured 100% of mice acutely infected with\n                    <jats:italic>Trypanosoma brucei brucei<\/jats:italic>\n                    CMP. With this model, the chemotherapeutic index of compound 2b was 512, compared to 256 for melarsamine dihydrochloride (Cymelarsan) under the same conditions. With a chronic infection produced by\n                    <jats:italic>T. brucei brucei<\/jats:italic>\n                    GVR, compound 2b cured 100% of mice after treatment at a dose of 25 \u03bcmol\/kg (12.5 mg\/kg) for 4 consecutive days, whereas melarsamine dihydrochloride and potassium melarsonyl (Trimelarsan) cured less than 50% mice at this dose. For both acute and late-stage infections, dithiaarsanes having a melaminophenyl ring exhibited the most-potent trypanocidal activity. Compound 2b is thus one of the most active organoarsenicals described in a mouse trypanosomiasis model. Considering that the main intracellular targets of organoarsenicals are thiol groups, we studied the possibility of ligand exchange between Cymelarsan and several dithiols. In aqueous solution, we observed a rapid exchange of cysteamine from melarsamine with free cysteamine and also with various dithiols always in favor of more stable cyclic derivatives. These ligand exchanges suggest the ability of trivalent organoarsenicals to react with targets such as trypanothione and dihydrolipoic acid. Among several ligands, a 1,3-dimercaptopropane moiety appeared the most suitable for trypanocidal activity.\n                  <\/jats:p>","DOI":"10.1128\/aac.44.11.2954-2961.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:06:42Z","timestamp":1027750002000},"page":"2954-2961","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Contribution of Dithiol Ligands to In Vitro and In Vivo Trypanocidal Activities of Dithiaarsanes and Investigation of Ligand Exchange in an Aqueous Solution"],"prefix":"10.1128","volume":"44","author":[{"given":"Philippe M.","family":"Loiseau","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Biologie et Contr\u00f4le des Organismes Parasites, UPRES 398, Universit\u00e9 de Paris-Sud, 92290 Ch\u00e2tenay-Malabry,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lubert","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Synth\u00e8se et Physicochimie Organique, UMR 5068 CNRS. Universit\u00e9 Paul Sabatier, 31400 Toulouse,2 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Gerard","family":"Wolf","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Synth\u00e8se et Physicochimie Organique, UMR 5068 CNRS. Universit\u00e9 Paul Sabatier, 31400 Toulouse,2 France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Apted\n              F. I. C.\n          Treatment of human trypanosomiasis\n          The African trypanosomiases.\n              Mulligan\n              H. W.\n          1970\n          684\n          710\n          George Allen\n          London United Kingdom"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.6.1298"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.8.2607"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(92)90024-E"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1949.s1-29.173"},{"key":"e_1_3_2_7_2","first-page":"245","article-title":"Melarsoprol in the treatment of African sleeping sickness.","volume":"115","author":"Friedheim E. A. H.","year":"1989","unstructured":"Friedheim E. A. H. Distefano D. Melarsoprol in the treatment of African sleeping sickness. Int. Sci. Council Tryp. Res. Control 115 1989 245 252","journal-title":"Int. Sci. Council Tryp. Res. 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Ngeranwa J. Kaminsky R. Preliminary observations on the efficacy of MelCy (Cymelarsan) in domestic animals infected with stocks of Trypanosoma brucei brucei and T. evansi. Trop. Med. Parasitol. 43 1992 226 228","journal-title":"Trop. Med. 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