title: Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy.
abstract: A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity againstin vitroandin vivoexperimental malaria models. Thein vitroabsorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India.
authors.forename: Vasantha Rao
authors.initials: VR
authors.lastname: Dola
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India.
authors.forename: Awakash
authors.initials: A
authors.lastname: Soni
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Division of Pharmaceutics, Central Drug Research Institute, Lucknow, India.
authors.forename: Hafsa
authors.initials: H
authors.lastname: Ahmad
authors.affiliation: Division of Pharmacokinetics and Metabolism, Central Drug Research Institute, Lucknow, India.
authors.forename: Kanumuri Siva Rama
authors.initials: KS
authors.lastname: Raju
authors.affiliation: Division of Pharmacokinetics and Metabolism, Central Drug Research Institute, Lucknow, India.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Division of Pharmacokinetics and Metabolism, Central Drug Research Institute, Lucknow, India.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wahajuddin
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India.
authors.forename: W
authors.initials: W
authors.lastname: Haq
authors.affiliation: Division of Pharmaceutics, Central Drug Research Institute, Lucknow, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Dwivedi
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India sb_katti@cdri.res.in.
authors.forename: S B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D000284:Administration, Oral; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006418:Heme / Q000037:antagonists & inhibitors / Q000378:metabolism; D006427:Hemin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D016789:Plasmodium cynomolgi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C047186:7-chloro-4-aminoquinoline; D006418:Heme; D006427:Hemin; D002738:Chloroquine
keywords: 4-aminoquinoline; antimalarial agents; chloroquine resistant; quinolines