title: Discovery of a bulky 2-tert-butyl group containing primaquine analogue that exhibits potent blood-schizontocidal antimalarial activities and complete elimination of methemoglobin toxicity.
abstract: To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against P. berghei and highly virulent multidrug-resistant P. yoelii nigeriensis strain in vivo. Compound 2 was also evaluated for methemoglobin (MetHb) toxicity. This study describes the discovery of a highly potent blood-schizontocidal antimalarial analogue 2, completely devoid of MetHb toxicity.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jain
authors.forename: Suryanarayana
authors.initials: S
authors.lastname: Vangapandu
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sachdeva
authors.forename: Savita
authors.initials: S
authors.lastname: Singh
authors.forename: Prati P
authors.initials: PP
authors.lastname: Singh
authors.forename: Gopa B
authors.initials: GB
authors.lastname: Jena
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
authors.forename: Poduri
authors.initials: P
authors.lastname: Ramarao
authors.forename: Chaman L
authors.initials: CL
authors.lastname: Kaul
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D008288:Malaria / Q000097:blood / Q000401:mortality / Q000469:parasitology; D008706:Methemoglobin / Q000032:analysis*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D010967:Plasmodium yoelii / Q000187:drug effects; D011319:Primaquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C482216:2-tert-butylprimaquine; D000962:Antimalarials; D008706:Methemoglobin; D011319:Primaquine