RESUMO
Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Fenol/farmacologia , Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Desenho de Fármacos , Antineoplásicos/química , Proliferação de Células , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.