Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents.
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.
Bhandari
Kalpana
K
Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226 001, India. kalpana_bhandari@cdri.res.in
Srinivas
Nagarapu
N
Marrapu
Vijay K
VK
Verma
Aditya
A
Srivastava
Saumya
S
Gupta
Suman
S
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
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