Banca de DEFESA: IGOR RESENDES BARBOSA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : IGOR RESENDES BARBOSA
DATE: 26/01/2021
TIME: 09:00
LOCAL: sala 50
TITLE:

Synthesis, Characterization and Biological Evaluation of Aryl-Sydnones and New Sulfonamide-Sydnone Hybrids

KEY WORDS:

Sydnones, sulfonamides, mesoionic

PAGES: 166
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Leishmaniasis are a group of diseases caused by parasites from the genus Leishmania. They are endemic in about 98 countries and territories and classified by WHO as Neglected Tropical Diseases. They affect thousands of people every year, causing high mortality and morbidity. Treatments for these parasitic infections are based on chemotherapy, with a small number of available drugs, which have several limitations, such as high costs, inconvenient and often painful route of administration and serious adverse effects. In addition the surge of resistance has become an emerging problem, with reported cases for all anti-leishmania substances of clinical use. In view of the very serious scenario created by leishmaniasis and the interest of our research group in mesoionic compounds and their biological activities, this dissertation presents the design and preparation of two series of sydnones with potential leishmanicidal activities: the first, composed of 13 simple N-aryl-sydnones and N-alkyl-sydnones (wich have already been reported in the literature), and the second, consisting of 8 novel sulfonamide sidnona hybrids. The first series of Sydnones was prepared in three steps, using the classic synthetic route widely described in the literature. The hybrids, in turn, were obtained by two additional steps, starting from the N-(4-nitro-phenyl)-sydnone or N-(3-nitro-phenyl)-sydnone. For this, the nitro group of these compounds was initially reduced using stannous chloride, yielding the N-(amino-phenyl)-sydnones. Finally, the sulfonamide-sydnone hybrids were obtained by maceration between the respective N-(amino-phenyl)-sydnones and the appropriate sulfonyl chlorides, in the presence of sodium carbonate and silica gel. The products were characterized by infrared spectroscopy, ¹H and ¹³C NMR. In the case of the novel compounds, two-dimensional NMR experiments (COSY, NOESY, HSQC, HMBC) were also performed to correctly assign all signals observed in the 1D ¹H and ¹³C spectra. This work proposes a viable rout for the preparation of sulfonamide-sidnones and presents a detailed discussion regarding the structural determination of these compounds and their synthetic intermadiates. All thirteen sydnones from the first series were evaluated in vitro against the promastigote form of L.amasonensis.  Os these, only the unsubstituted phenyl-sydone and those containing a nitro group in the benzene ring showed IC₅₀ values below the highest concentration tested (< 128 µM). The N-(3-nitro-phenyl)-sydnone was the most potent compound, with an IC₅₀ of 18.22 µM.

BANKING MEMBERS:
Presidente - 387189 - AUREA ECHEVARRIA AZNAR NEVES LIMA
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Interna - 1177598 - ROSANE NORA CASTRO
Externo à Instituição - LUIZ CARLOS DA SILVA PINHEIRO
Externa à Instituição - Roberta Katlen Fusco marra - UFRJ