title: Ivermectin-derived leishmanicidal compounds.
abstract: In the present study a family of macrocyclic and acyclic analogues as well as seco-analogues of avermectins were prepared from commercial Ivermectin (IVM) and their antileishmanial activity assayed against axenic promastigote and intracellular amastigote forms of Leishmania amazonensis. Contrarily to the filaricidal activity, the leishmanicidal potentiality of avermectin analogues does not appear to depend on the integrity of the non-conjugated Delta(3,4)-hexahydrobenzofuran moiety. Conjugated Delta(2,3)-IVM or its corresponding conjugated secoester show higher anti-leishmania activity than the parent compound. Surprisingly, the diglycosylated northern sub-unit exhibits the same anti-amastigote potentiality as the southern hexahydrobenzofuran. As expected for compounds derived from the widely used Ivermectin antibiotic, little toxicity has been noticed for most of the novel analogues prepared.
authors.affiliation: Instituto de Química, Universidade Federal do Rio de Janeiro, Ilha do Fundão, CT, Bloco A, CEP 21941-909, Rio de Janeiro, RJ, Brazil.
authors.forename: Anderson Rouge
authors.initials: AR
authors.lastname: dos Santos
authors.forename: Camila Alves Bandeira
authors.initials: CA
authors.lastname: Falcão
authors.forename: Michelle Frazão
authors.initials: MF
authors.lastname: Muzitano
authors.forename: Carlos Roland
authors.initials: CR
authors.lastname: Kaiser
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Férézou
mesh_terms: D000818:Animals; D001572:Benzofurans; D004187:Disaccharides; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D007894:Leishmania mexicana / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D001572:Benzofurans; D004187:Disaccharides; D014344:Trypanocidal Agents; D007559:Ivermectin; C019264:avermectin; C105430:benzofuran