title: 4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.
abstract: Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Singh
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India; Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India.
authors.forename: Drishti
authors.initials: D
authors.lastname: Agarwal
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.affiliation: Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.affiliation: Department of Zoology, University of Delhi, Delhi 110007, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India.
authors.forename: Rinkoo D
authors.initials: RD
authors.lastname: Gupta
authors.affiliation: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: satishpna@gmail.com.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Awasthi
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D002738:Chloroquine / Q000494:pharmacology*; D003362:Cost-Benefit Analysis; D004351:Drug Resistance / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D010966:Plasmodium vivax / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D002738:Chloroquine; D007770:L-Lactate Dehydrogenase; C001920:4-aminoquinoline
keywords: 4-Aminoquinoline analogues; Amodiaquine; Antimalarial; Chloroquine; Plasmodium berghei; Plasmodium falciparum