Orally active esters of dihydroartemisinin: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice.
A series of artemisinin derived esters 7a-j, incorporating pharmacologically privileged substructure, such as biphenyl, adamantane and fluorene, have been prepared and evaluated for antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis by oral route. Several of these compounds were found to be more active than the antimalarial drugs beta-arteether 4 and artesunic acid 5. Ester 7i, the most active compound of the series, provided 100% and 80% protection to the infected mice at 24 mg/kg x 4 days and 12 mg/kg x 4 days, respectively. In this model beta-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.
Singh
Chandan
C
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, India.
Chaudhary
Sandeep
S
Puri
Sunil K
SK
D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008958:Models, Molecular; D010967:Plasmodium yoelii / Q000254:growth & development; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D001713:Biphenyl Compounds; D004952:Esters; D012717:Sesquiterpenes; C039060:artenimol; D000218:Adamantane; C055141:artemotil