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Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action
Authors:La-Scalea M A  Chin C M  Cruz M L  Serrano S H  Ferreira E I
Institution:1. Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, USP, Av. Prof. Lineu Prestes, 580, 05508-900, São Paulo, Brazil;2. Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, UNESP/Araraquara, C.P. 502, 14801-902, São Paulo, Brazil;3. Departamento de Farmácia, Faculdade de Ciências Médicas, PUCCAMP, C.P. 1111, 13059-740, São Paulo, Brazil;4. Departamento de Quı́mica Fundamental, Instituto de Quı́mica, USP, C.P. 26077, 05599-970 São Paulo, Brazil;2. Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany;3. Department of Cardiology, Thorax Institute Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain;4. Center for Cardiac Arrhythmias of Genetic Origin–IRCCS Istituto Auxologico Italiano, Milan, Italy;5. Klinikum Esslingen GmbH, Abteilung Kardiologie, Esslingen, Germany;11. Vivantes Klinikum Neukölln, Berlin, Germany;12. Corporació Sanitària Parc Taulí de Sabadell, Sabadell, Spain;8. St. George’s University, London, United Kingdom;9. Division of Geriatric Cardiology and Medicine, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy;112. Menarini Ricerche S.p.A, Florence, Italy;123. Menarini Industrie Farmaceutiche Riunite s.r.l, Florence, Italy;1. Department of Medicinal Chemistry, AstraZeneca India Pvt. Ltd, Bellary Road, Hebbal, Bangalore 560024, India;2. Organic and Medicinal Chemistry Research Laboratory, Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India;1. College of Physics and Materials Science, Henan Key Laboratory of Photovoltaic Materials, Henan Normal University, Xinxiang 453007, China;2. College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, Shanxi 030024, China;1. PK-PD, Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India;2. Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu, India;3. Clinical Microbiology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India;4. Drug Theoretics and Chemoinformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India;5. Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India;6. Director, CSIR-Indian Institute of Integrative Medicine, Jammu, India;1. Chongqing Key Laboratory of Inorganic Functional Materials, Department of Scientific Research Management, Chongqing Normal University, Chongqing, 401331, China,;2. College of Materials Science and Engineering, Chongqing University, Chongqing, 400044, China,;3. Chongqing Key Laboratory of Catalysis and New Environmental Materials, College of Environment and Resources, Chongqing Technology and Business University, Chongqing, 400067, China;4. The Center for Environmental Monitoring, Dianjiang County, Chongqing 408300, China;5. Key Laboratory of Green Catalysis of Sichuan Institutes of High Education, Sichuan University of Science and Technology, Zigong 643000, China;1. Pharmacokinetic Research Laboratories, Ono Pharmaceutical Company, Ltd., Ibaraki, Japan;2. Sugiyama Laboratory, RIKEN Innovation Center, RIKEN, Kanagawa, Japan;3. Oncology Clinical Development Planning, Ono Pharmaceutical Company, Ltd., Osaka, Japan;4. Translational Medicine Center, Ono Pharmaceutical Company, Ltd., Osaka, Japan
Abstract:This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.
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