Tukulula M., Little S., Gut J., Rosenthal P.J., Wan B., Franzblau S.G., Chibale K.
The design, synthesis, in silico ADME profiling, antiplasmodial and antimycobacterial evaluation of new arylamino quinoline derivatives
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom; Department of Medicine, San Francisco General Hospital, University of San Francisco, CA 94143, United States; Institute of Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, IL 60612-7231, United States; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa
Tukulula, M., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Little, S., London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom; Gut, J., Department of Medicine, San Francisco General Hospital, University of San Francisco, CA 94143, United States; Rosenthal, P.J., Department of Medicine, San Francisco General Hospital, University of San Francisco, CA 94143, United States; Wan, B., Institute of Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, IL 60612-7231, United States; Franzblau, S.G., Institute of Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, IL 60612-7231, United States; Chibale, K., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa
A series of new arylamino quinoline derivatives was designed based on the quinine and mefloquine scaffolds and evaluated in vitro for antiplasmodial and antimycobacterial activities. A number of these compounds exhibited significant activity against the drug-sensitive 3D7 and drug-resistant K1 strains of Plasmodium falciparum. Furthermore, two compounds, 4.12b and 4.12d, also showed 94 and 98% growth inhibitory activity against non-replicating and replicating Mycobacterium tuberculosis strains, respectively. © 2012 Elsevier Masson SAS. All rights reserved.
4 [(1 tert butyl 1h tetrazol 5 yl)(piperidin 1 yl)methyl] 6 methoxyquinoline; antimalarial agent; n [(1 tert butyl 1h tetrazol 5 yl)(6 methoxyquinolin 4 yl)methyl] n ethylethanamine; quinoline derivative; tuberculostatic agent; unclassified drug; antibacterial activity; antiprotozoal activity; article; computer model; drug absorption; drug design; drug distribution; drug excretion; drug metabolism; drug structure; drug synthesis; electrospray mass spectrometry; growth inhibition; in vitro study; Mycobacterium tuberculosis; nonhuman; physical chemistry; Plasmodium falciparum; Aminoquinolines; Antiprotozoal Agents; Antitubercular Agents; Biological Assay; Blood-Brain Barrier; Computer Simulation; Drug Design; Erythrocytes; Humans; Inhibitory Concentration 50; Mefloquine; Microbial Sensitivity Tests; Models, Biological; Mycobacterium tuberculosis; Plasmodium falciparum; Quinine; Structure-Activity Relationship; Tetrazoles