ABSTRACT
INTRODUCTION: Canis lupus familiaris is a domestic dog and many owners consider their pets as a family member. Medical bills with dogs are overcame only by the health care received by humans. Medical care is constantly progressing, and so is veterinary care. Metabolomics is the ''omic" technique aimed to the study of metabolome, low-molecular weight molecules, through biofluids or tissue samples. And it also allows to evaluate disease diagnosis and prognosis, therapeutic evaluation and toxicological studies. OBJECTIVES: The goal of this paper is to review the current and potential applications of metabolomics in domestic dogs. METHOD: ScienceDirect, Scopus, Reaxys and PubMed were searched for papers that performed canine metabolomics in any research area. RESULTS: We analysed 38 papers, published until April 2019 in canine metabolomics approach. Metabolomic research in dogs so far can be divided into three areas: (a) Metabolomics studies in veterinary science, such as improving pet dogs health and welfare. (b) Diet, breeds and species discrimination. (c) Use of dogs as animal model in different diseases and drug development (evaluation toxicity and effect). CONCLUSIONS: The results of this review showed that interest in metabolomics is growing in veterinary research. Several canine diseases have been evaluated with some promise for potential biomarker and/or disease mechanism discovery. Because canine metabolomics is a relatively new area, the researches spread across different research areas and with few studies in each area.
Subject(s)
Dogs/metabolism , Metabolomics , AnimalsABSTRACT
Herein, we describe the C4-ethoxylation of 2,4-dichloroquinoline to prepare 2-chloro-4-ethoxy-quinoline (3), which is a prominent intermediate used for the synthesis of 2-substituted quinolones. To achieve this goal, we studied different conditions for the reaction between 2,4-dichloroquinoline and sodium ethoxide. We discovered that the use of 18-crown-6 ether as an additive and dimethylformamide as the reaction solvent allowed us to obtain the desired product 3 in very good yield and selectivity. In addition, a definitive distinction between the C2 and C4 ethoxylation products was achieved using 1 Hâ15 N heteronuclear multiple bond correlation. Compound 3 is an intermediate used for the synthesis of 2-((3-aminopropyl)amino)quinolin-4(1H)-one, which displays peculiar behavior during 1 H nuclear magnetic resonance analysis, such as the broadening of the H8 singlet and unexpected deuteration at the C8-position. Effort has been dedicated to understand these findings.
ABSTRACT
The combination of tools such as time-kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8-hydroxy-5-quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8-hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time-kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time-kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non-irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.
