title: New orally active amino- and hydroxy-functionalized 11-azaartemisinins and their derivatives with high order of antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice.
abstract: By use of artemisinin 1 as the starting material, two new amino- and hydroxy-functionalized 11-azaartemisinins 9 and 11 and their derivatives 12a-g, 13a-g, 14a-g, and 15a-c have been prepared and screened for antimalarial activity by oral route against multidrug-resistant Plasmodium yoelii in Swiss mice. While azaartemisinins 9 and 11 showed only modest activity, several of their derivatives showed high order of antimalarial activity. Biphenyl-based compound 13f, the most active compound of the series, provided 100% and 80% protection to the infected mice at 12 mg/kg × 4 days and 6 mg/kg × 4 days, respectively. Compounds 12f, 13b, 13e, 13g, and 14f showed 100% protection at 12 mg/kg × 4 days, while compounds 12a-c, 14a, 14c-e, 14g, and 15a-c showed similar levels of protection at 24 mg/kg × 4 days. Clinically useful drug β-arteether provided 100% protection at 48 mg/kg × 4 days and 20% protection at 24 mg/kg × 4 days in this model.
authors: Division of Medicinal and Process Chemistry and ‡Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226001, India.
authors: Chandan
authors: C
authors: Singh
authors: Ved Prakash
authors: VP
authors: Verma
authors: Mohammad
authors: M
authors: Hassam
authors: Ajit Shankar
authors: AS
authors: Singh
authors: Niraj K
authors: NK
authors: Naikade
authors: Sunil K
authors: SK
authors: Puri
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D001372:Aza Compounds; D007202:Indicators and Reagents; C031327:artemisinin