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Identification of potential molecular targets related to cancer for the formicamycin’s family

Identification of potential molecular targets related to cancer for the formicamycin’s family

Bruna Schuck de Azevedo and Rafael Andrade Caceres

According to the Global Cancer Observatory, 18 million new cases and 9.5 million deaths were estimated for all types of cancer in 2018. The World Health Organization predicts that in 2030 there will be a 70% increase in new cases and 45% in deaths. Due to the rise of cancer incidence and mortality, it is necessary to invest in the discovery and development of new antineoplastic drugs. The novel family of molecules called formicamycin, active against some antibiotic-resistant microorganisms, had a tyrosine kinase enzyme predicted as one of its molecular targets. As this enzyme plays a role in the progression of cancer, the potential antineoplastic action of the formicamycins has been studied. In order to identify the potential molecular targets for an antineoplastic action of the compounds of the formicamycin family, a reverse virtual screening (RVS) was performed using two web servers, PharmMapper and SwissTargetPrediction, to establish the potential targets which interact with them. The targets obtained concomitantly on both servers had their influence on carcinogenesis verified through a literature review in PubMed. The binding energy between target and compound was determined for the targets that seemed to influence carcinogenesis through simulations of molecular docking, with Autodock 4.2 and Autodock Vina, and molecular dynamics, with the GROMACS v.4.6.7 package. Fifteen potential molecular targets were obtained at the intersection of the two RVS servers used. In the literary review, twelve of them were associated with carcinogenesis. These twelve molecular targets were subjected to molecular docking and molecular dynamics simulations. At the end of the RVS process, three potential molecular targets for the formicamycins were identified. Among these macromolecules, nuclear receptor subfamily 1 group I member 2 and matrix metalloproteinase 3 are the most promising targets for an antineoplastic action of these compounds.