Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines |
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| Institution: | 1. Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia, and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain;2. Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom;3. Bradford School of Pharmacy, University of Bradford, West Yorkshire BD7 1 DP, United Kingdom;4. Department of Pharmaceutics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;5. Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, 08193-Bellaterra, Barcelona, Spain;1. Alchemical Research, LLC, 260 East Wall Street, Bethlehem, PA 18018, USA;2. Division of Pharmaceutical Sciences, School of Pharmacy, and Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA;1. Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia;2. Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati, Maharashtra 444 602, India;3. Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan;1. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China;2. University of Chinese Academy of Sciences, Beijing 100049, PR China;3. College of Life Sciences, Sichuan University, Chengdu 610064, PR China;1. Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia, and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, E-08028 Barcelona, Spain;2. Departament de Fisicoquímica, Facultat de Farmàcia (Campus Torribera), and IBUB, Universitat de Barcelona, Prat de la Riba 171, E-08921 Santa Coloma de Gramenet, Spain;4. Departament de Farmacologia, de Terapèutica i de Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Barcelona, Spain;5. Laboratori de Química Orgànica, Facultat de Farmàcia, Universitat de Barcelona, and Barcelona Science Park, Baldiri Reixac 10-12, E-08028 Barcelona, Spain |
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| Abstract: | We have synthesized a series of dimers of (+)-(7R,11R)-huprine Y and evaluated their activity against Trypanosoma brucei, Plasmodium falciparum, rat myoblast L6 cells and human acetylcholinesterase (hAChE), and their brain permeability. Most dimers have more potent and selective trypanocidal activity than huprine Y and are brain permeable, but they are devoid of antimalarial activity and remain active against hAChE. Lead optimization will focus on identifying compounds with a more favourable trypanocidal/anticholinesterase activity ratio. |
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| Keywords: | Molecular dimerization Trypanocidal agents Antimalarial agents Bis(4-aminoquinolines) Brain permeability |
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