Natural Dibenzo [b,f] oxepines, Pacharin and Bauhiniastatin-1, Isolated from Bauhinia acuruana Induce Apoptosis on Breast Cancer Cells via MCL-1 Protein Reduction Silvia de Maria Souza, Luciano Santos de Souza, Valdenizia Rodrigues Silva, Milena Botelho Pereira Soares, Daniel Pereira Bezerra, et al. Planta Medica, 2023 Herein, we describe the antiproliferative effects of two natural dibenzo [b,f]oxepines, pacharin and bauhiniastatin-1, isolated from Bauhinia acuruana on a breast cancer cell line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by the MTT assay, and IC50 values ranged from 7.8 to 45.1 µM, including human breast adenocarcinoma (MCF-7) cells. In contrast, none of the compounds were cytotoxic on normal human peripheral blood mononuclear cells (IC50 > 100 µM). Human breast adenocarcinoma (MCF-7) cells treated with pacharin or bauhiniastatin-1 20 µM for 24 h presented a reduction in cell volume and intensification of chromatin condensation, DNA fragmentation, and apoptotic cells. These findings became more evident after 48 h of exposure. Antiapoptotic B-cell lymphoma-2 family members, such as myeloid cell leukemia-1 and B-cell lymphoma-extra large, are important targets in cancer cells since their overexpression confers resistance to cancer treatments. A significant reduction of the myeloid cell leukemia-1 protein levels in human breast adenocarcinoma (MCF-7) cells after 24 h of treatment with pacharin or bauhiniastatin-1 at 20 µM was observed, while the B-cell lymphoma-extra large protein content was reduced in bauhiniastatin-1-treated cells at 40 µM only. The cytotoxic effects of pacharin and bauhiniastatin-1 are likely linked to myeloid cell leukemia-1 inhibition, which leads to the apoptosis of breast adenocarcinoma cells.
Synthesis and Anticancer Activity of Homodimeric Morita-Baylis-Hillman Adducts Based on 3-Hydroxyindolin-2-one Core Maísa Coelho, Aleff Castro, Tayná Olegário, Rodrigo Cristiano, Boniek Vaz, et al. Journal of the Brazilian Chemical Society, 2023 Cancer treatment represents one of the main scientific study targets today, mainly due to the pronounced side effects arising from chemotherapy. This study reports the synthesis, characterization, and anticancer activity of ten compounds from the Morita-Baylis-Hillman reaction. Ethylene glycol diacrylate was used as a double Michael acceptor in reactions with isatin derivatives to give homodimers of 3-hydroxyindolin-2-one core, recognized in the literature for its extensive pharmacological profile. The use of 1,4-diazabicyclo[2,2,2]octane (DABCO) as a catalyst and room temperature were the optimal conditions for the study reaction. The isolated yields were up to 63%, with most reaction times inferior to 24 h, some as fast as 15 min. The anticancer potential of the synthesized dimers was evaluated in vitro against three cancer strains, resulting in average inhibitory concentrations up to 0.72 μM. It was also found that the best performing homodimers are more active than their monomeric counterparts. Considering the promising selectivity indices observed, the preliminary results obtained here act as a basis for broader tests regarding the effectiveness of homodimeric adducts against cancer cells.
Synthesis, cytotoxic and antimicrobial activities of 5-benzylidene-2-[(pyridine-2-ylmethylene)hydrazono]-thiazolidin-4-one derivatives Latin American Journal of Pharmacy, 2012
Cytotoxic flavonoids from Platymiscium floribundum Maria José C. Falcão, Yvone Brígido M. Pouliquem, Mary Anne S. Lima, Nilce Viana Gramosa, Letícia V. Costa-Lotufo, et al. Journal of Natural Products, 2005