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Bioorg Med Chem ; 17(2): 496-502, 2009 Jan 15.
Article in English | MEDLINE | ID: mdl-19114308

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.


Subject(s)
Ivermectin/analogs & derivatives , Ivermectin/chemistry , Trypanocidal Agents/chemical synthesis , Animals , Benzofurans , Disaccharides , Ivermectin/chemical synthesis , Ivermectin/pharmacology , Ivermectin/toxicity , Leishmania mexicana/drug effects , Macrophages/drug effects , Macrophages/parasitology , Mice , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanocidal Agents/pharmacology , Trypanocidal Agents/toxicity
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