| Grant number: | 18/12062-4 |
| Support Opportunities: | Regular Research Grants |
| Start date: | September 01, 2018 |
| End date: | May 31, 2021 |
| Field of knowledge: | Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry |
| Principal Investigator: | Pedro Paulo Corbi |
| Grantee: | Pedro Paulo Corbi |
| Host Institution: | Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| City of the host institution: | Campinas |
Abstract
Several diseases caused by bacteria of different species, as well as those caused by some types of viruses, such as influenza and dengue, are a case of concern. Epidemiological data estimate 3 to 5 million cases of influenza per year and approximately 290 to 650 thousand deaths. The symptoms caused by severe cases of influenza are similar to the symptoms caused by dengue fever, which is a viral infection transmitted by mosquitoes and can cause severe complications. Dengue fever has been increasing progressively in recent decades and an estimated 390 million cases are reported each year in more than 100 countries, exposing nearly half of the world's population to a situation of risk. In the search for new pharmacologically active complexes, a particular interest has been given to the interaction of metals with already known and established antibacterial drugs, such as sulfonamides, and with those used as antivirals such as adamantane derivatives. Thus, the combination of biologically active ligands and metals of well-known antimicrobial action may result in novel drug candidates with differentiated mechanisms of action and activities on microorganisms at different stages of cell growth. Such compounds could also lead to a decrease in the possibility of the emergence of microbial resistance when compared to free drugs. In this project, the synthesis and characterization of Ag(I), Cu(II), Pt(II) and Pd(II) complexes with the sulfonamides mafenide and sulfamethazine will be discussed, as well as the preparation of complexes with adamantane derivatives , such as rimantadine and amantadine. The complexes will be characterized by a set of chemical and spectroscopic techniques, with emphasis on infrared and nuclear magnetic resonance spectroscopic measurements, X-ray diffraction of single-crystals and high-resolution mass spectrometry. The compounds will be evaluated for their antibacterial activities on a set of Gram-positive and Gram-negative strains, determining the minimum inhibitory concentration values, with emphasis on the action on Mycobacterium tuberculosis. Antiviral activities, especially on species that cause diseases such as influenza, dengue, zika and chikungunya will be evaluated by the molecular RT-PCR method, quantifying the viral loads. Subsequently, cytotoxicity studies on different cell types will be performed to evaluate the safety, selectivity and potential of application of the compounds of interest. The active compounds will be submitted to procedures of interaction with biomolecules such as DNA and proteins to evaluate their potential biological targets. (AU)
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