The molecular mechanisms underlying the observed anticancer effects of flavonoids remain unclear. Increasing evidence shows that the aryl hydrocarbon receptor (AHR) plays a crucial role in neoplastic disease progression, establishing it as a potential drug target. This study evaluated the potential of hydroxy flavonoids, known for their anticancer properties, to interact with AHR, both in silico and in vitro, aiming to understand the mechanisms of action and identify selective AHR modulators. A PAS-B domain homology model was constructed to evaluate in silico interactions of chrysin, naringenin, quercetin apigenin and agathisflavone. The EROD activity assay measured the effects of flavonoids on AHR’s activity in human breast cancer cells (MCF7). Simulations showed that chrysin, apigenin, naringenin, and quercetin have the highest AHR binding affinity scores (−13.14 to −15.31), while agathisflavone showed low scores (−0.57 and −5.14). All tested flavonoids had the potential to inhibit AHR activity in a dose-dependent manner in the presence of an agonist (TCDD) in vitro. This study elucidates the distinct modulatory effects of flavonoids on AHR, emphasizing naringenin’s newly described antagonistic potential. It underscores the importance of understanding flavonoid’s molecular mechanisms, which is crucial for developing novel cancer therapies based on these molecules.

Tuberculose é uma doença infecciosa causada pelo Mycobacterium tuberculosis que continua sendo uma das principais causas de morte por doença infecciosa. Este estudo teve como objetivo a identificação de potenciais inibidores da pantotenato sintetase, enzima essencial para a bactéria, através de triagem virtual hierárquica. Modelos baseados na forma e volume moleculares foram construídos e validados para filtrar um banco de dados com estruturas químicas produtos naturais. As moléculas selecionadas foram acopladas na estrutura do alvo molecular, obtido junto ao Protein Data Bank sob o código 3IUB com o programa FRED. O composto ZINC000012489800 foi a mais bem ranqueada. As interações intermoleculares mostraram interações hidrofóbicas, ligações de hidrogênio (aceptoras e doadoras) e iônicas, entre o composto identificado e aminoácidos importantes para o reconhecimento molecular já descritas na literatura. A molécula possui parâmetros farmacocinéticos razoáveis e bom índice de segurança toxicológico. Este estudo demonstra a eficácia dos métodos in silico na identificação de um composto promissor para o tratamento da tuberculose multirresistente, representando um passo importante na busca por novas terapias. Referências Bloom B, et al. Tuberculosis. Major Infect Dis. 2017;6(3):233-313. DOI: 10.1596/978-1-4648-0524-0_ch11. Moreira AD, Kritsk AL, Carvalho AC. Social determinants of health and catastrophic costs associated with the diagnosis and treatment of tuberculosis. J. Bras. de Pneumol. 23 fev 2020; 46(5): e20200015. DOI: 10.36416/1806-3756/e20200015. World Health Organization. Tuberculosis [Internet]; [citado 19 out 2023]. Available from: https://www.who.int/health-topics/tuberculosis#tab=tab_1. World Health Organization. Global Tuberculosis Report [Internet]. Geneva: WHO [citado 19 out 2023]. 68p. 2022. 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