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Bioinformatics approach on bioisosterism softwares to be used in drug discovery and development

Author(s):

Nelson José Freitas da Silveira*, Walter Filgueira de Azevedo Jr., Rita Cardoso Guedes, Leandro Marcos Santos, Rodolfo Cabral Marcelino, Patrícia Antunes and Thiago Cabral Elias  

Abstract:


Background: In the rational drug development field, a bioisosterism is a tool that improves lead compounds performance, reffering to molecular fragment substitution that has similar physical-chemical properties. Thus, it is possible to modulate drug properties such as absorption, toxicity, and half-life increase. This modulation is of pivotal importance in the discovery, development, identification, and interpretation of the mode of action of biologically active compounds.

Objective: Our purpose here is to review the development and application of bioisosterism in drug discovery. In this study history, applications, and use of bioisosteric molecules to create new drugs with high binding affinity in the protein-ligand complexes are described.

Method: It is an approach for molecular modification of a prototype based on the replacement of molecular fragments with similar physicochemical properties, being related to the pharmacokinetic and pharmacodynamic phase, aiming at the optimization of the molecules.

Results: Discovery, development, identification, and interpretation of the mode of action of biologically active compounds are the most important factors for drug design. The strategy adopted for the improvement of leading compounds is bioisosterism.

Conclusion: Bioisosterism methodology is a great advance for obtaining new analogs to existing drugs, enabling the development of new drugs with reduced toxicity, in a comparative analysis with existing drugs. Bioisosterism has a wide spectrum to assist in several research areas.

Keywords:

Protein-Ligand Interaction, Bioisosterism, Computational Chemistry, Medicinal Chemistry, Structural Bioinformatics, pharmacokinetic.

Affiliation:

Laboratory of Molecular Modeling and Computer Simulation, Department of Exact Science, Federal University of Alfenas/UNIFAL-MG, Alfenas, Laboratory of Computational Systems Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, The Research Institute for Medicines (iMed.Ulisboa) and Department of Pharmaceutical Chemistry and Therapeutics, Faculty of Pharmacy, University of Lisbon, Lisboa, Laboratory of Molecular Modeling and Computer Simulation, Department of Exact Science, Federal University of Alfenas/UNIFAL-MG, Alfenas, Laboratory of Molecular Modeling and Computer Simulation, Department of Exact Science, Federal University of Alfenas/UNIFAL-MG, Alfenas, Laboratory of Molecular Modeling and Computer Simulation, Department of Exact Science, Federal University of Alfenas/UNIFAL-MG, Alfenas, Laboratory of Molecular Modeling and Computer Simulation, Department of Exact Science, Federal University of Alfenas/UNIFAL-MG, Alfenas



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