title: Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents.
abstract: A series of aryloxy alkyl/aryl alkyl imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani. All the 19 compounds exhibited 94-100% inhibition at 10microg/mL against promastigotes and 12 compounds exhibited high inhibition with an IC(50) in the range of 0.47-4.85microg/mL against amastigotes. Promising compounds were tested further in vivo. Among all, compounds 4 and 23 with 4-CF(3) aryloxy moiety exhibited medium in vivo inhibition of 58-60%, thus providing new structural lead for antileishmanials.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226 001, India. kalpana_bhandari@cdri.res.in
authors.forename: Kalpana
authors.initials: K
authors.lastname: Bhandari
authors.forename: Nagarapu
authors.initials: N
authors.lastname: Srinivas
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Marrapu
authors.forename: Aditya
authors.initials: A
authors.lastname: Verma
authors.forename: Saumya
authors.initials: S
authors.lastname: Srivastava
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000953:Antigens, Protozoan / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003510:Cyclohexanes / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000981:Antiprotozoal Agents; D003510:Cyclohexanes; D007093:Imidazoles; D008565:Membrane Proteins; D015800:Protozoan Proteins; C072094:surface antigen P2, Leishmania; C506365:Cyclohexane; C106989:amastigote surface protein-1; D009439:Neuraminidase