Prospecção in silico de moléculas identificadas em extratos citotóxicos contra células tumorais de bactérias marinhas da Amazônia Azul

Abstract

Complex diseases, such as cancer, are among the leading causes of death around the world. As they have several pathways involved in their pathogenesis, these diseases could respond well to molecules which bind to more than one therapeutic target. From this perspective, natural products (NPs) are an important source of molecules, because these molecules usually have a multi-target nature, which is useful as medicine for a variety of diseases. The discover and development of new drugs is expensive and time-consuming and can take decades from the identification of the active compound until its approval by regulatory agencies. Thus, in silico approaches can contribute to the investigation of bioactive compounds, allowing the identification of several possible targets concurrently. MicroMarin is a marine bacterial collection with approximately 1,400 strains from the Blue Amazon, the Brazilian Economic Exclusive Zone. Approximately 15% of the organic extracts of bacteria from MicroMarin tested so far showed cytotoxic activity against tumor cells. This work aimed to carry out the survey, cataloging and investigation, through target fishing, molecular targets of NPs of marine origin belonging to MicroMarin. Ninety-seven molecules of at least 17 chemical classes were identified, identified among 30 bacteria strains. The three platforms used for protein targets through target fishing, TargetNet, MolTarPred and PassOnline, allowed the identification of a total of 2662 targets. Among the large number of possible targets, molecules that interacted with targets in more than one database with interaction probability >90 were chosen. Some interesting hits were Cyclo (Trp-trans-Pro) and Cyclo (Trp-cis-Pro) diketopiperazines interacted with the kappa-type opioid receptor. Additionally, staurosporine, hydroxy-staurosporine, Nmethyl- staurosporine, N-methyl-hydroxy-staurosporine and N-carboxamidestaurosporine interacted with five kinase-like proteins. This in silico prospection of pharmacological potential added greater biotechnological potential to the bank. Further studies to assess the interaction between target and ligand, as well as its biological relevance, need to be conducted to confirm the results obtained here.