A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent
| العنوان: | A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent |
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| المؤلفون: | Caroline de Souza Pereira, Romulo Ivisson Santos De Deus Da Silva, Diana Fontinha, Diogo Rodrigo Magalhães Moreira, Vinicius Schmitz, William Rodrigo Avendaño Castro, Milena Botelho Pereira Soares, Bruno Pradines, Helenita C. Quadros, Maribel Navarro, Isabelle Fonta, Joel Mosnier, Mathieu Gendrot, Miguel Prudêncio, Hélio F. Dos Santos |
| المساهمون: | Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Repositório da Universidade de Lisboa |
| المصدر: | ChemMedChem ChemMedChem, Wiley-VCH Verlag, 2021, 16 (4), pp.662-678. ⟨10.1002/cmdc.202000653⟩ ChemMedChem, 2021, 16 (4), pp.662-678. ⟨10.1002/cmdc.202000653⟩ Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Plasmodium berghei, media_common.quotation_subject, Plasmodium falciparum, Heme, Primaquine, 01 natural sciences, Biochemistry, Antimalarials, Structure-Activity Relationship, Parasitic Sensitivity Tests, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, General Pharmacology, Toxicology and Pharmaceutics, ComputingMilieux_MISCELLANEOUS, media_common, Pharmacology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Organic Chemistry, Chloroquine, DNA, Art, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, 3. Good health, Malaria, 010404 medicinal & biomolecular chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Gold, Humanities |
| الوصف: | © 2020 Wiley‐VCH GmbH Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ-gold(I) hybrid molecule affects essential parasite targets, it inhibits β-hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ-gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood-stage of Plasmodium falciparum and liver-stage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple-stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malaria. This work was supported by the Brazilian funding agencies: CAPES(grant no. 23038.006713/2013-88), CNPq (grant no. 305732/2019-6), FAPES grant number APP0088/2016) and Fiocruz/Inova (grant no.1642178247). MP was supported by grant PTDC-SAU-INF-29550-2017 (FCT,Portugal). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1860-7179 1860-7187 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::154f94eb05c789f3cfb272654760c5e9 https://hal-amu.archives-ouvertes.fr/hal-03160988 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....154f94eb05c789f3cfb272654760c5e9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18607179 18607187 |
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