Bisindolylmaleimides New Ligands of CaM Protein
Por:
Sosa-Peinado, Alejandro, Fructuoso-Garcia, Karina, Vasquez-Bochm, L. X., Gonzalez-Andrade, Martin
Publicada:
1 ene 2022
Resumen:
In the present study, we reported the interactions at the molecular level of a series of compounds called Bisindolylmaleimide, as potential inhibitors of the calmodulin protein. Bisindolylmaleimide compounds are drug prototypes derived from Staurosporine, an alkaloid with activity for cancer treatment. Bisindolylmaleimide compounds II, IV, VII, X, and XI, are proposed and reported as possible inhibitors of calmodulin protein for the first time. For the above, a biotechnological device was used (fluorescent biosensor hCaM M124C-mBBr) to directly determine binding parameters experimentally (Kd and stoichiometry) of these compounds, and molecular modeling tools (Docking, Molecular Dynamics, and Chemoinformatic Analysis) to carry out the theoretical studies and complement the experimental data. The results indicate that this compound binds to calmodulin with a Kd between 193–248 nM, an order of magnitude lower than most classic inhibitors. On the other hand, the theoretical studies support the experimental results, obtaining an acceptable correlation between the GExperimental and GTheoretical (r2 = 0.703) and providing us with complementary molecular details of the interaction between the calmodulin protein and the Bisindolylmaleimide series. Chemoinformatic analyzes bring certainty to Bisindolylmaleimide compounds to address clinical steps in drug development. Thus, these results make these compounds attractive to be considered as possible prototypes of new calmodulin protein inhibitors. © 2022 by the authors.
Filiaciones:
Sosa-Peinado, Alejandro:
Laboratorio de Biosensores y Modelaje Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Fructuoso-Garcia, Karina:
Laboratorio de Biosensores y Modelaje Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Vasquez-Bochm, L. X.:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Gonzalez-Andrade, Martin:
Laboratorio de Biosensores y Modelaje Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
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