Criação e validação de inibidores baseados em triterpenóides provenientes da Euphorbia tirucalli com potencial anti-inflamatório contra a câncer colorretal através de métodos in sílico

Abstract

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide, caused by altered signaling pathways that promote immune evasion. Proteins from these signaling pathways, such as COX-2 (cyclooxygenase-2), STAT3 (signal transducers and activators of transcription), and NF-kB (nuclear factor kappa B), are therapeutic targets studied against hyperinflammatory pro-oncogenic factors in various tumors. However, classical chemotherapy treatments often result in broad side effects. As a result, the scientific community has been seeking new, less toxic chemotherapeutic agents derived from natural plant compounds. In this study, Euphorbia tirucalli is presented as a source of bioactive compounds, such as triterpenoids, which have anti-inflammatory and antitumor potential. Therefore, the objective is the design of unique triterpenoid molecules from E. tirucall to target inflammation causing CRC using in silico methods like CADD (Computer-Aided Drug Design), which includes SBDD (Structure-Based Drug Design) — docking and molecular dynamics — and LBDD (Ligand-Based Drug Design), involving small molecule alignment, pharmacophore, and scaffold hopping. Seven triterpenoids were selected and screened through molecular docking with inflammatory molecules such as COX-2, STAT3, and NF-kB. The docking studies demonstrated promising binding energy values with the constructed molecules compared to existing drugs, yielding acceptable pharmacokinetic results. Finally, the triterpenoids from Euphorbia tirucalli proved useful for the construction of unique molecules, predicting antitumor and anti-inflammatory potential against CRC.