title: New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice.
abstract: A new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl-based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24 mg/kg × 4 days as well as 12 mg/kg × 4 days, respectively. In this model β-arteether provided 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively.
authors.affiliation: Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India; Materials Research Centre, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India; Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: schaudhary.chy@mnit.ac.in.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Chaudhary
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Niraj K
authors.initials: NK
authors.lastname: Naikade
authors.affiliation: Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India.
authors.forename: Mohit K
authors.initials: MK
authors.lastname: Tiwari
authors.affiliation: Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Yadav
authors.affiliation: Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India.
authors.forename: Bharti Rajesh K
authors.initials: BRK
authors.lastname: Shyamlal
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: sk_puri@cdri.res.in.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004952:Esters / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010967:Plasmodium yoelii / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004952:Esters; C039060:artenimol
keywords: 1,2,4-Trioxanes; Antimalarial; Arteether; Dihydroartemisinin; Multi-drug resistant