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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

An electronic point of view on the inhibition of ALK-5 by bioactive candidates related to cancer

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Author(s):
Almeida, Michell O. [1, 2] ; Faria, Sergio H. D. M. [3, 4] ; Honorio, Kathia M. [2, 5]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Inst Quim Sao Carlos, Ave Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil
[2] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas, Rua Santa Adelia 166, BR-09210170 Santo Andre, SP - Brazil
[3] Univ Estadual Campinas UNICAMP, Inst Quim, Rua Josue de Castro 126, Cidade Univ, BR-13083861 Campinas, SP - Brazil
[4] Univ Paulista UNIP, Av Comendador Enzo Ferrari 280, BR-13045770 Campinas, SP - Brazil
[5] Univ Sao Paulo Ciencias & Humanidades, Escola Artes, Av Arlindo Bettio 1000, BR-03828000 Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: THEORETICAL CHEMISTRY ACCOUNTS; v. 139, n. 5 MAY 6 2020.
Web of Science Citations: 0
Abstract

Cancer is a very complex disorder, and it is urgent to find new ways to treat it. This study aims to evaluate the inhibition mechanism of ALK-5 (target related to breast cancer) from an electronic point of view. Computational simulations (QM/MM, NBO, QTAIM) were performed, and the ONIOM method (B3LYP/cc-pVDZ:UFF) was used to obtain the optimized geometries of the studied systems. The NBO analyses indicated that the most important electron transfer occurs between LP N (inhibitor 1) and BD{*} O-H (Tyr249) orbitals (Delta E-2 = 11.89 kcal/mol). The weakest interaction occurs between the LP N (inhibitor 4) and BD{*} N-H (His283) orbitals (Delta E-2 = 0.81 kcal/mol). The QTAIM analyses suggested that the most active inhibitors perform a greater number of hydrogen bonds with the major residues. Therefore, quantum mechanics methods proved to be important to better understand the inhibition of ALK-5, as well as helping the design of new inhibitors. (AU)

FAPESP's process: 14/27189-9 - Theoretical study of the interaction between bioactive ligands and TGF-² receptor type 1 (ALK-5) using methods of molecular modeling
Grantee:Michell de Oliveira Almeida
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/24524-7 - STRUCTURAL ANALYSIS AND MOLECULAR MODELING STUDIES FOR NATURAL AND SYNTHETIC LIGANTS RELATED TO NEGLECTED DISEASES
Grantee:Kathia Maria Honorio
Support type: Regular Research Grants
FAPESP's process: 17/10118-0 - Study and application of electrochemical technology for the analysis and degradation of endocrine interferents: materials, sensors, processes and scientific dissemination
Grantee:Marcos Roberto de Vasconcelos Lanza
Support type: Research Projects - Thematic Grants