DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Benzophenone derivatives showed dual anti-inflammatory and antiproliferative activities by inhibiting cox enzymes and promote cyclin e downregulation.(2022) Folquitto, Laís Regina dos Santos; Souza, Thiago Belarmino de; Januário, Jaqueline Pereira; Nascimento, Isadora M.; Brandão, Brenda Tavares de Vasconcelos; Moreira, Maria E. C.; Horvath, Renato de Oliveira; Santos, Marcelo Henrique dos; Coelho, Luiz Felipe Leomil; Veloso, Marcia Paranho; Soares, Marisi Gomes; Carvalho, Diogo Teixeira; Ionta, Marisa; Paula, Daniela Aparecida Chagas de; Dias, Danielle FerreiraConsidering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo anti- inflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7)showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA-MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.Item Phenylpropanoid-based sulfonamide promotes cyclin D1 and cyclin E downregulation and induces cell cycle arrest at G1/S transition in estrogen positive MCF-7 cell line.(2019) Barbosa, Helloana Azevedo; Silva, Guilherme Álvaro Ferreira da; Silva, Carolina Faria; Souza, Thiago Belarmino de; Dias, Danielle Ferreira; Paula, Ana Cláudia Chagas de; Ionta, Marisa; Carvalho, Diogo TeixeiraCancer is one of the most critical problems of public health in the world and one of the main challenges for medicine. Different biological effects have been reported for sulfonamide-based compounds including antibacterial, antifungal, and antitumor activities. Herein, a series of phenylpropanoid-based sulfonamides (4a, 4a′, 4b, 4b′, 5a, 5a′, 5b and 5b′) were synthesized and their cytotoxic activity was evaluated against four cell lines derived from human tumours (A549 – lung, MCF-7 – breast, Hep G2 - hepatocellular carcinoma, and HT-144-melanoma). Cell viability was significantly reduced in the MCF-7 cell line when compounds 4b, 4b′ and 5a were used; IC50 values were lower than those found for their precursors (eugenol and dihydroeugenol) and sulfanilamide. We observed that 4b induced cell cycle arrest at G1/S transition. This is probably due to its ability to reduce cyclin D1 and cyclin E expression. Moreover, 4b also induced apoptosis in MCF-7 cells as demonstrated by an increase in the cell population positive for annexin V in treated cultures in comparison to the control group. Taken together, the data showed that 4b is a promising antitumor agent and it should be considered for further in vivo studies.