Deborah de Alencar Simoni

Arboviral diseases such as Zika, Mayaro and chikungunya fevers are neglected infections transmitted by arthropod vectors. The search for alternatives to circumvent the effects of arboviruses by modifying molecules previously known for their antiviral activities can be considered a good strategy to obtain new antiviral drugs. Here, we describe the synthesis of novel adamantane‑derived Schiff bases and their antiviral activities against Zika (ZIKV), Mayaro (MAYV) and chikungunya (CHIKV) viruses. Amantadine Schiff base was prepared by reaction of amantadine and 2-thiophenecarboxyaldehyde (atdTiof), while rimantadine Schiff base was prepared by reaction of rimantadine and 5-fluoro-2-hydroxybenzaldehyde (rtdFhba). The compositions of the Schiff bases were determined by elemental and mass spectrometric analyses as C15H19NS and C19H24FNO for atdTiof and rtdFhba, respectively. Spectroscopic characterizations added to single crystal X-ray diffraction permitted proposing the structures of Schiff bases. Cell viability and antiviral activities of the compounds were evaluated against ZIKV, MAYV and CHIKV viruses. The atdTiof and rtdFhba species exhibited the best inhibition rates of 58.5% over ZIKV and 69.5% over CHIKV, respectively. The results obtained in the in vitro studies open perspectives for future in vivo investigations of the synthesized Schiff bases in the search for alternatives for the treatment of arboviruses.

Em princípio, um composto de coordenação mononuclear (também conhecido como complexo) é um arranjo formado pela interação de um íon (ou átomo) metálico central, chamado de “núcleo”, com átomos, íons ou moléculas ao seu redor, chamados “ligantes”. O número de ligantes que formam ligações coordenadas é denominado número de coordenação, que depende da configuração eletrônica do íon (ou átomo) central, da sua carga e do seu tamanho, entre outros fatores. Neste experimento didático, o objetivo é determinar o número de coordenação e a constante global de formação do complexo diamino-prata(I), utilizando a técnica de titulação por precipitação. Isso pode ser feito calculando as concentrações de íons prata não complexados presentes em misturas preparadas com quantidades constantes de íons prata(I) e quantidades crescentes de amônia. As concentrações remanescentes de íons [Ag⁺] em solução são determinadas por meio da titulação com uma solução padronizada de íons brometo. Embora a parte experimental pareça ser de execução simples, a prática exige habilidades técnicas para o manuseio correto dos instrumentos básicos utilizados em um laboratório de análises e o conhecimento sobre funções logarítmicas. Além disso, a interpretação dos resultados requer alguns conhecimentos teóricos, como o conceito de ácidos e bases de Lewis, o entendimento dos fenômenos de solubilidade e do produto de solubilidade, dos balanceamentos de carga e de massa e das constantes de formação dos complexos. O processamento dos dados experimentais e a construção de gráficos são conhecimentos essenciais.

Deoxygenative olefinations enable access to expand the chemical space of chiral pools by installing a carbon-carbon double bond. We explored methodologies to remove oxygenated functionalities along with the formation of an olefin, applying the formation of an enol triflate followed by a hydrogenolysis in the synthesis of stachene diterpenoids (+)-monogynol, (+)-monogynoic acid, and (+)-nidoanomalin.

Platinum(II) and palladium(II) complexes have been investigated as potential anticancer drugs since the serendipitous discovery of the antineoplastic activities of cisplatin in the 1960s. Skin cancer is considered the most common malignant neoplasm that affects humans, and melanoma is the most lethal type of skin cancer. Surgical excision is the main form of treatment, which also may include radiotherapy, systemic chemotherapy, and immunotherapy. In this work, new insights concerning the structural characterization and in vitro anti-proliferative activity of the palladium(II) complex with the amino acid deoxyalliin (Pd-sac) against a panel of thirteen human tumor cells, with emphasis on skin cancer cell lines, are presented. The composition of the complex was confirmed by elemental analysis as [Pd(C₆H₁₀NO₂S)₂]. The structure of the complex was elucidated for the first time by a single-crystal X-ray diffraction technique. Each deoxyalliin molecule coordinates in a bidentate N,S-mode to palladium(II) in a trans-configuration analogous to the platinum(II) deoxyalliin complex early reported. As the main result, the Pd-sac complex showed a selective anti-proliferative activity against melanoma (UACC-62, TGI = 63.5 µM), while both deoxyalliin and K₂PdCl₄ were inactive against all cell lines. Moreover, Pd-sac did not affect the proliferation of non-tumorigenic keratinocytes (HaCaT, TGI > 586 µM) and was non-mutagenic in the Ames assay. The results open new perspectives for in vivo studies concerning the application of the Pd-sac complex in the treatment of melanoma.