Estudo da toxicidade, docking molecular e efeito do sm-2 em modelo pré-clínico no câncer de língua em camundongos

Abstract

The World Health Organization (WHO) reveals that a large part of the world's population, between 60% and 80%, has already used herbal medicines to treat various diseases. Products from plants generally contain fewer adverse reactions to the human body. Medicinal plants such as S. maritima are considered an interesting alternative for scientific studies on their medicinal potential. Stemodia maritima Linn is a plant called (known as matruz-bravo or melosa), used for different empirical applications in alternative medicine by people from the coastal area of northeastern Brazil in Ceará. The S. maritima and estemodane derivatives have been the target of study by researchers due to their rare chemical structure and bioactive compounds. In particular, a diterpene derivative called Stemodin (Sm-1), a product derived from the leaves of S. maritima. Research with Sm-1 emonstrated that Sm-1 has analgesic, gastroprotective, bactericidal and cytotoxic activity. From Sm-1, two other semi-synthetic stemodane derivatives with biological potential were developed: SM-2 and SM-3. The methodology of studies carried out with SM-2 in animal models with experimentation used Swiss mice (males and females) for evaluation of Acute toxicity with SM-2 at a dose of 2000µg/kg according to OECD protocol nº425. Furthermore, the study included molecular docking analyzes of SM-2, using specific software for the in silico analysis of the protein structures of several ligand target molecules, such as: TNF-α (PDB: 1TNF), 1L-1β (PDB: 1ITB ), HO-1 (PDB: 1N3O), iNOS (PDB: 3NQS), TRPV1 Receptor (PDB: 5IS0), P2X7 Receptor (PDB: 5U1W) and opioid receptors: Mu (µ) (PDB: 4DK1), Kappa (K) (PDB: 4DJH) and Delta (δ) (PDB:6PT3) ligand targets with pharmacokinetic potential. In the study in question, another investigation of the SM-2 compound was conducted in an in vivo model using C57/BL6 mice (males and females) using the chemical substance 4-nitroquinoline (4-NQO), a cancer-inducing agent. of squamous cells on the tongue -CCE. The animals received 4-NQO for 10 weeks, and after 8 weeks of suspension of 4-NQO, treatment with SM-2 (oral and topical on the tongue) was started for 12 consecutive weeks. The protocol lasted a total of 32 weeks, until the animals were euthanized. The objective of the study was to evaluate the anti-inflammatory and antitumor potential in carcinogenesis in SCC. The results were expressed as mean ± standard error of the mean (SEM). The results obtained in the study with histopathological analysis of the tongue emonstrated that SM-2 may be a promising therapeutic option in the treatment of tongue cancer. And the analysis of statistical data was analyzed by Shapiro-Wilk, post-test Tukey and GamesHowell test and Mann Whitney T test (nonparametric) for ANOVA (p-value < 0.05). Therefore, research on SM-2, an stemodane derivative, reveals remarkable therapeutic potential, especially in the context of inflammation associated with tongue cancer