title: Anilino-(2-bromophenyl) acetonitrile: a promising orally effective antileishmanial agent.
abstract: Visceral leishmaniasis (VL) or kala-azar is a worldwide disseminated intracellular infection caused by the hemoflagellate protozoan parasites Leishmania donovani. Chemotherapeutic scenario presents a deplorable picture and demands an urgent search for a new and safe anti-VL drugs, preferably active by oral route. In search of new antileishmanial agents, a total of 16 compounds belonging to the anilino-(substituted phenyl)-acetonitrile class were tested in vitro in promastigote/macrophase-amastigote systems and in vivo in L. donvoani/hamster model for their antileishmanial activity. Compound 3, anilino-(2-bromophenyl)-acetonitrile, exhibited most promising activity both in vitro at a concentration of 100 microg/ml (82.33 and 94.36% in promastigote and macrophase-amastigote systems, respectively) and in vivo at a dose of 50 mg/kg for 5 days (82.11 and 80% by i.p. and p.o. routes, respectively), hence this compound was investigated in detail. To maximize its bioavailability, dissolution profile, absorption, the compound was also tested in vivo as its soluble form. But no enhancement in activity was observed. From the results of different parameters for example ED(50) and LD(50) etc. compound 3 appears to be a potent orally effective compound which could further be investigated to establish its potential as a candidate molecule of antileishmanial therapy.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, 226001, Lucknow, India. gupta_suman@yahoo.com
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.forename: Suman
authors.initials: S
authors.lastname: Tiwari
authors.forename: A P
authors.initials: AP
authors.lastname: Bhaduri
authors.forename: G K
authors.initials: GK
authors.lastname: Jain
mesh_terms: D000097:Acetonitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D007928:Lethal Dose 50; D008297:Male; D008647:Mesocricetus; D016896:Treatment Outcome
chemical_list: D000097:Acetonitriles; D000981:Antiprotozoal Agents; C471355:anilino-(2-bromophenyl)acetonitrile