EVALUACIÓN DE BIOISÓSTEROS DE LA DOXORRUBICINA EN LA ESTABILIDAD DE COMPLEJOS LIGANDO-PARP1, CDK2 Y αPI3K

Elian Guaillazaca Gonzales

doi:10.47187/perf.v1i33.312

Authors

Elian Guaillazaca Gonzales Escuela Superior Politécnica de Chimborazo, Facultad de Ciencias, Riobamba, Chimborazo, Ecuador

DOI:

https://doi.org/10.47187/perf.v1i33.312

Keywords:

PARP1, αPI3K, CDK2, Molecular Docking, Bioisosteres, Design of new drugs

Abstract

This study focused on the evaluation of doxorubicin bioisosteres and their impact on the stability of ligand-protein complexes, specifically PARP1, CDK2, and αPI3K. A computational approach was used to investigate these molecular docking interactions. The aim of this study is to understand how bioisosteres can offer more stable interactions with cancer-related proteins, thereby increasing treatment effectiveness. The methodology involved generating potential bioisosteres from doxorubicin to then perform molecular docking analysis between ligand complexes. Therefore, the affinity and stability of these bioisosteres were evaluated using molecular docking techniques. The results obtained showed that the bioisosteric complexes generated presented significantly more stable interactions with the proteins compared to the original doxorubicin. In particular, bioisosteres B5 and B4 showed better interaction, with binding energies of -11,62 and -8,29 kcal/mol, respectively, for the PARP1 and CDK2 proteins, suggesting that they could be promising candidates for the development of new treatments. The optimization of these compounds could significantly contribute to the development of more effective and less toxic therapies for the treatment of breast cancer.

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