Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species.
Fabíola Suelen Dos SantosRossimiriam Pereira de FreitasCamila Simões de FreitasDébora Vasconcelos Costa MendonçaDaniela Pagliara LageGrasiele de Sousa Vieira TavaresAmanda Sanchez MachadoVivian Tamieti MartinsAdilson Vidal CostaVagner Tebaldi de QueirozMariana Belizario de OliveiraFabrício Marques de OliveiraLuciana Maria Ribeiro AntinarelliElaine Soares CoimbraEduardo Jorge PilauGeovane Perez da SilvaEduardo Antônio Ferraz CoelhoRobson Ricardo TeixeiraPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania . Currently, there is no human vaccine, and the available treatments are associated with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28 , N -((1-(7-(diethylamino)-2-oxo-2 H -chromen-3-yl)-1 H -1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis -infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL.
Keyphrases
- magnetic resonance
- infectious diseases
- oxidative stress
- high resolution mass spectrometry
- reactive oxygen species
- induced apoptosis
- endothelial cells
- liquid chromatography
- oxide nanoparticles
- escherichia coli
- diabetic rats
- mass spectrometry
- electronic health record
- magnetic resonance imaging
- big data
- room temperature
- signaling pathway
- gas chromatography
- plasmodium falciparum
- current status
- high resolution
- cell cycle arrest
- artificial intelligence
- induced pluripotent stem cells
- cell death
- deep learning
- data analysis