SÍNTESE DE DERIVADOS TRIAZÓLICOS DO ÁCIDO CAFEÍCO

O ácido cafeíco demonstrou interessante atividade antiproliferativa contra linhagens de células cancerígenas testadas, sobretudo para células do colo do útero. Sharpless definiu “Click Chemistry” como uma abordagem de ampla aplicação para ser utilizada na preparação de uma série de substâncias com grande diversidade química. Os triázois são compostos heterocíclicos que possuem 3 átomos de nitrogênio em um mesmo núcleo cíclico, de origem exclusivamente sintética, não ocorrendo na natureza. Esta classe de compostos vem despertando interesse pela ampla aplicação, inclusive em relação à atividade antitumoral. Neste trabalho está descrita a preparação de novos derivados triazólicos do ácido cafeíco, via cicloadição 1,3-dipolar de Huisgen, através da conjugação entre o ácido cafeíco e azidas funcionalizadas, e a caracterização das moléculas formadas a partir da análise RMN de ¹

Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher

Synthetic naphthoquinone derivatives as anticancer agents in ovarian cancer: cytotoxicity assay and investigation of possible biological mechanisms action

In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their in vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3–5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4, bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3–5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK