title: 8-quinolinamines and their pro prodrug conjugates as potent blood-schizontocidal antimalarial agents.
abstract: Synthesis and antimalarial activities of N8-(4-amino-1-methylbutyl)-5-alkoxy-4-ethyl-6-methoxy-8-quinolinamines (5) and their pro prodrug analogues (6-7) prepared by covalently linking 5 to the redox-sensitive (8) and esterase-sensitive (9) linkers through the amide linkage are reported. The most effective 8-quinolinamines [5c (R=C5H11) and 5f (R=C8H17)] have exhibited in vitro and in vivo biological efficacy superior to that of the standard drug chloroquine against both drug-sensitive and drug-resistant malaria strains. Analogues 6-7 were evaluated for in vivo blood-schizontocidal activity as potential pro prodrug models for the primary amino group containing 8-quinolinamines (5). The most effective pro prodrug analogue (6c) has displayed promising activities against drug-sensitive and drug-resistant strains of Plasmodia in vivo.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Suryanarayana
authors.initials: S
authors.lastname: Vangapandu
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sachdeva
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jain
authors.forename: Savita
authors.initials: S
authors.lastname: Singh
authors.forename: Prati Pal
authors.initials: PP
authors.lastname: Singh
authors.forename: Chaman Lal
authors.initials: CL
authors.lastname: Kaul
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008288:Malaria / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D000634:Aminoquinolines; D000962:Antimalarials; D011355:Prodrugs; C080436:8-aminoquinoline