Synthesis of an organo-ruthenium aminoquinoline-trioxane hybrid and evaluation of its activity against Plasmodium falciparum and its toxicity toward normal mammalian cells
| Autor: | Alberto Martínez, Christiane Deregnaucourt, Joseph Schrevel, Véronique Sinou, Christine Latour, Roberto A. Sánchez-Delgado, Dipankar Roy |
|---|---|
| Přispěvatelé: | Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Chemistry Department of Brooklyn College and Ph.D. Program in Chemistry, CUNY Graduate Center (The Graduate Center), City University of New York [New York] (CUNY)-City University of New York [New York] (CUNY), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Chemistry Department, City University of New York [New York] (CUNY)-Brooklyn College [CUNY], City University of New York [New York] (CUNY)-The Graduate Center, Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ketone Trioxane chemistry.chemical_element 01 natural sciences Aminoquinoline 03 medical and health sciences chemistry.chemical_compound Ruthenocene medicine Moiety [CHIM]Chemical Sciences General Pharmacology Toxicology and Pharmaceutics Artemisinin ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification biology 010405 organic chemistry Organic Chemistry Plasmodium falciparum biology.organism_classification Combinatorial chemistry 3. Good health 0104 chemical sciences Ruthenium 030104 developmental biology [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology chemistry medicine.drug |
| Zdroj: | Medicinal Chemistry Research Medicinal Chemistry Research, 2017, 26 (2), pp.473-483. ⟨10.1007/s00044-016-1769-6⟩ Medicinal Chemistry Research, Springer Verlag, 2017, 26 (2), pp.473-483. ⟨10.1007/s00044-016-1769-6⟩ |
| ISSN: | 1054-2523 1554-8120 |
| DOI: | 10.1007/s00044-016-1769-6⟩ |
| Popis: | A new hybrid compound 5 containing a ruthenocene, a 4-aminoquinoline, and a 1,2,4-trioxane within a single molecular structure has been synthesized and evaluated for antimalarial potential. In order to ascertain the role of each component of hybrid 5, its antimalarial activity has been measured against chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum in comparison with those of chloroquine, artemisinin, a ruthenocene-trioxane compound 9 not containing an aminoquinoline, the precursor trioxane ketone 4, and a trioxane dimer 10. Hybrid 5 displays high antimalarial activity, in the mid to low nanomolar IC50 range, and low cytotoxicity toward healthy mammalian cells, which translates into good selectivity indexes. The potency of 5 is consistently higher than those of chloroquine, the parent metal-free trioxane, and compound 9, the structural intermediate featuring a ruthenocene moiety bound to the trioxane but lacking the aminoquinoline. These results validate our hypothesis that it is the combination of the aminoquinoline, the ruthenocenyl moiety, and the trioxane in a single molecule that provides the enhanced antiplasmodial activity, and highlight the concept of hybrid compounds as a strategy that deserves further attention. |
| Databáze: | OpenAIRE |
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