title: Design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents.
abstract: A series of substituted aryl pyrimidine derivatives was synthesized and evaluated in vitro for their antileishmanial potential against intracellular amastigotes of Leishmania donovani using reporter gene luciferase assay. Among all, 8 compounds showed promising IC50 values ranging from 0.5 to 12.9 μM. Selectivity indices (S.I.) of all these compounds are far better than reference drugs, sodium stibogluconate (SSG) and miltefosine. On the basis of good S.I., compounds were further screened for their in vivo antileishmanial activity against L. donovani/hamster model. Compounds 2d, 4a and 4b have shown significant inhibition of parasitic multiplication that is 88.4%, 78.1% and 78.2%, respectively at a daily dose of 50 mg/kg × 5 days, when administered intraperitoneally. Compound 2d is most promising one, which may provide a new lead that could be exploited as a new antileishmanial agent.
authors.affiliation: Division of Medicinal Chemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, India. shivajins@yahoo.co.in
authors.forename: S N
authors.initials: SN
authors.lastname: Suryawanshi
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Rahul
authors.initials: R
authors.lastname: Shivahare
authors.forename: Susmita
authors.initials: S
authors.lastname: Pandey
authors.forename: Avinash
authors.initials: A
authors.lastname: Tiwari
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D011743:Pyrimidines; C030986:pyrimidine
keywords: Hamster; In vitro; In vivo; Leishmania donovani; Luciferase assay; Pyrimidines