2025-02-282021-02-26BARBOSA, Helloana Azevedo. Síntese e estudos da relação estrutura-atividade e dos mecanismos de ação de aril-sulfonamidas derivadas de fenilpropanoides frente às linhagens provenientes de adenocarcinoma de mama humana. 2021. 150 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Alfenas, Alfenas, MG, 2021.https://repositorio.unifal-mg.edu.br/handle/123456789/2520A study recently published by our research group showed that novel aryl-sulfonamide derivatives, obtained by the molecular hybridization from eugenol and dihydroeugenol, had promising antiproliferative activity on cells derived from breast adenocarcinoma (MCF-7). Derivative 4b altered the dynamics of cell cycle progression and induced arrest in the G1/S transition. This effect was correlated with a reduction in the protein levels of cyclins D1 and E. Furthermore, 4b demonstrated pro-apoptotic activity on MCF-7 cells. Therefore, to understand the structure-activity relationship (SAR) that modulates the antiproliferative activity of 4b on tumor cells, the synthesis of nine structural analogues (HAB 1 to 9) was proposed. Thus, in addition to investigating the mechanisms of action associated with the antiproliferative activity of 4b on MCF-7 cells, the present study aimed to: a) Synthesize the structural analogues HAB 1 to 9; b) Evaluate the cytotoxicity of HAB 1 to 9 on MCF-7, MDA-MB 231, Hs 578T and HepG2 cells; and c) Establish SAR studies between 4b and the proposed structural analogues with the observed in vitro biological activity. HAB 1 to 9 were successfully obtained, and their structures confirmed by IR, NMR and MS analyses. The results showed that against MCF-7 and MDA-MB 231 cell lines, HAB 1, 2 and 4 efficiently reduced the viability of the treated cultures, whereas in HepG2 cell line HAB 2 and 9 were the most effective. Since the reduction in viability of MDA-MB 231 cultures treated with HAB 2 and 4 in preliminary studies was higher than 50 %, these two substances were selected for characterization of the antiproliferative and/or cytotoxic profile, where it was observed that HAB 2 was the most promising derivative of the series. HAB 2 promoted morphological changes and on the dynamics of cell cycle progression of MDA-MB 231 cultures, inducing arrest in the G1/S transition. Taken together, the results demonstrated that phenylpropanoid-sulfonamide hybrid 4b and its structural analog HAB 2 present new chemical structures and exhibited a promising antiproliferative activity profile against MCF-7 and MDA-MB 231 cultures, respectively. 4b and its analogue HAB 2 can be considered to compose in vivo studies, in search of validating the antitumor potential against estrogen receptor positive and triple negative breast cancer, respectively.application/pdfAcesso AbertoFenilpropanoidesAril-sulfonamidasHibridação molecularAtividade antiproliferativaCâncer de mamaCIENCIAS DA SAUDE::FARMACIATeseCarvalho, Diogo Teixeira