Estudo in silico do potencial antifúngico de compostos de Cenostigma pyramidale (TUL.)

Abstract

Studies on the therapeutic properties of plants are important in the search for new compounds that may have effective biological activities and fewer adverse effects. The species endemic to the Brazilian Northeast, Cenostigma piramidale (Tul.), known as “Catingueira”, is widely used in traditional medicine to treat fungal infections. Several metabolites of medicinal value have been reported in C. piramidale, mostly flavonoids and biflavonoids. Fungal infections cause approximately 1.5 million deaths annually and are a growing challenge due to resistance to common antifungal drugs, azoins. These drugs inhibit the enzyme Lanosterol 14-α-demethylase, essential for the synthesis of ergosterol. Inhibition of ergosterol, a crucial steroid for fungi, impairs their cell membranes. This study aims to investigate the antifungal potential of secondary metabolites of C. piramidale through molecular docking. For the development of the study, the crystallographic structure of the fungal enzyme LDM (PDB ID: 4WMZ) was obtained from the Protein Data Bank and treated using the Discovery Studio and AutoDockTools software. From a literature review, 14 metabolites of C. piramidale (Tul.) reported in previous studies were designed and optimized using the MarvinSketch program. Molecular docking was performed using the Autodock Vina software coupled with PyRx. The interactions resulting from the enzyme-ligand complexes formed were evaluated using the Discovery Studio program. The results showed that nine of the metabolites contained a binding layer by the 4WMZ receptor. Free energy calculations indicated projected values for new compounds, six of which reported a higher binding layer compared to the co-crystallized ligand fluconazole. The complexes formed between the enzyme and the tested metabolites resulted mainly from hydrophobic and Van der Waals interactions. In addition, stronger hydrogen bond interactions were observed, contributing to greater stabilization of the complexes. Some biflavonoids, due to their high molecular weight, obtained positive ΔG values, making the interaction between these metabolites and the target not spontaneous. The research carried out in the present study suggests that the molecules tested have promising antifungal activity and, based on the in silico analysis performed, are promising candidates for future pharmacokinetic and pharmacodynamic studies.