Banca de QUALIFICAÇÃO: FELIPE FERNANDO BEZERRA SANTIAGO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : FELIPE FERNANDO BEZERRA SANTIAGO
DATE: 23/04/2026
TIME: 09:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

Development, identification, and in silico structural modification of antithrombotic compounds that inhibit the P2Y12 protein.

KEY WORDS:

Fragment-Based Drug Design; Fragment growing; Therapeutic target; Molecular docking.

PAGES: 141
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

The discovery of bioactive molecules has been driven by computational approaches and rational strategies, such as Fragment-Based Drug Design (FBDD) and fragment growing techniques. In the context of cardiovascular diseases, membrane-bound therapeutic targets are consolidated as vital for the prevention of severe thrombotic disorders. Aiming at new therapeutic alternatives, the series of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide com pounds exhibit significant antiplatelet activity. Driven by this scenario, the present work aimed to develop in silico novel inhibitor candidates for this therapeutic target, using the triazole de rivative 2a as a starting point. Methodologically, the research involved the development of the software Ligands by brute force substituent replacement (LigBrs) for in silico structural modi fication and automated generation of the candidate library, coupled with the implementation of a Python tool for molecular docking automation. Following system preparation, the novel mol ecules were docked into the receptor. Subsequently, molecular dynamics simulations and bind ing free energy calculations using the MMPBSA method were performed for refined screening. Finally, the validated virtual structures were used in a three-dimensional similarity search, em ploying the LS-align algorithm. The results demonstrated that the fragment growing strategy via LigBrs generated derivatives with optimized conformations and higher predicted binding affinity. Thermodynamic validation (MMPBSA) and molecular dynamics confirmed the gain in stability and active site interactions compared to the control molecule 2a. The most prominent virtual prototype, LIG16, was utilized for prospective screening via LS-align in the ZINC22 database, culminating in the identification of three commercially available and structurally vi able analogs: ZINCsL00000gnB0E, ZINCsq000005Qvl5, and ZINCsG000008o5Y0. It is con cluded that the integration of these computational tools demonstrated high efficacy in the ra tional expansion of chemical space, providing solid candidates for therapeutic target inhibition that can be directly employed in future synthesis proposals and in vitro experimental assays.

COMMITTEE MEMBERS:
Presidente - 2378605 - CRISTIANE FERNANDES DE ASSIS
Externa à Instituição - ESTELA MARIANA GUIMARÃES LOURENÇO - UFMG
Externo à Instituição - LEONARDO BRUNO FEDERICO - UFSC