title: Synthesis and biological evaluation of a novel series of aryl S,N-ketene acetals as antileishmanial agents.
abstract: A series of aryl S,N-ketene acetals 7(a-f) was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. All the 6 compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC50 values ranging from 1.2 to 3.5 μM and were found promising as compared with reference drugs, sodium stibogluconate (SSG) and paromomycin. On the basis of good selectivity indices (SI), they were further tested for their in vivo potential against L. donovani/hamster model. Two compounds 7a and 7b showed significant inhibition of parasite multiplication, 72% and 83%, respectively. These compounds were comparable with SSG and superior to paromomycin. Preliminary in vitro metabolic investigations were also performed to assess the metabolic stability and in vitro hepatic intrinsic clearance (Clint) of compound 7b in hamster liver microsomes.
authors.affiliation: Division of Medicinal Chemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, P.O. Box 173, Mahatma Gandhi Road, Lucknow 226001, India. shivajins1952@gmail.com
authors.forename: S N
authors.initials: SN
authors.lastname: Suryawanshi
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Avinash
authors.initials: A
authors.lastname: Tiwari
authors.forename: Rahul
authors.initials: R
authors.lastname: Shivahare
authors.forename: Yashpal Singh
authors.initials: YS
authors.lastname: Chhonker
authors.forename: Susmita
authors.initials: S
authors.lastname: Pandey
authors.forename: Nishi
authors.initials: N
authors.lastname: Shakya
authors.forename: Rabi Sankar
authors.initials: RS
authors.lastname: Bhatta
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005030:Ethylenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000080:Acetals; D000977:Antiparasitic Agents; D005030:Ethylenes; D007659:Ketones; C008223:ketene