Dengue fever is a serious disease acquired from the Aedes aegypti mosquito present in tropical and subtropical regions, deeply impacting the population's quality of life. Its control requires combating the virus, and the use of substances that do not cause damage to the environment is of fundamental importance. The present work was carried out in silico to perform the structural-electronic characterization of the alkaloid Methylcytisine, a tricyclic quinolizidine alkaloid that has insecticidal activities, identifying the molecular boundary orbitals and descriptors of global chemical reactivity and assessing the inhibitory potential of methylcytisine on NS5 methyltransferase enzyme dengue virus, as well as identifying possible biological targets in humans. Methylcytisine was geometrically optimized through semi-empirical quantum calculations with thermodynamically more stable conformation, characterizing its structure (atoms, angles and bonds) and its reactivity descriptors. The analysis of the molecular docking simulations showed that methylcytisine is coupled in the same active site of the NS5 enzyme methyltransferase DENV, very similar to the complexed ligand S-adenosyl-L-homocysteine. The intermolecular interactions found for the complex formed and the distance values of the enzyme residues, indicate that methylcytisine has potential application as a new inhibitor of the dengue virus, however it has a high possibility of interaction with human neuronal acetylcholine receptors.
Currently, the search for new drugs with greater therapeutic potential and less side effects has been fostered by the advancement of the use of molecular modeling drugs, which in addition to supporting the full characterization of the molecule, allow simple algorithms to predict pharmacokinetic. In this context the present work aimed to perform the electronic / structural characterization, to evaluate the pharmacokinetic properties and to perform a virtual screening of the possible biological targets of Sophoraflavonone G, a promising flavonone, which presents several pharmacological properties. Sophoraflavanone G was geometrically optimized by semi-empirical quantum calculations, plot the MESP, identifying the nucleophilic sites. Using the boundary orbitals, it was possible to identify a greater tendency for electron donation in relation to Naringeni, with lower ionization potential, higher hardness and less softness. With respect to pharmacokinetics Sophoraflavonone G confirmed the safety of the compound for oral administration with good skin permeability, which allows applications in topical formulations. Presents indications for gastro intestinal absorption, as for possible interactions with biological targets, interaction with the estrogen receptor alpha, sodium / glucose co-transporter 2, beta-secretase 1, cyclooxygenase-1.The data obtained from an early stage for a comparative analysis between its analogues and fundamental for future studies of relationships between the three-dimensional structure of Sophoraflavanone G and its biological activities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.