Structural insights into the biological activity of a thioxopyrimidine derivative.
J Mol Model
; 27(3): 73, 2021 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-33547505
Bacterial resistance to the main widespread antibiotics, such as those based on quinolones, is a concern of the scientific community, leading to the search for new classes of molecules that can be used as an alternative. Here, we investigate the crystalline and chemical characteristics of a thioxopyrimide to understand its demonstrated biological activity and to identify which portion of the molecule can be used as a framework to develop new antibiotics. For this purpose, structural studies of ethyl 4-methyl-2-phenyl-6-thioxo-1,6-dihydro-5-pyrimidinecarboxylate were carried out aided by Hirshfeld surface analysis, as well as theoretical calculations on frontier molecular orbitals, molecular electrostatic potential, and conformational stability, in addition to docking studies targeting topoisomerase IV. The docking results show a reasonable accommodation of the molecule at the topoisomerase IV binding site and interact mainly by hydrogen bonds between the thioxopyrimidine portion with Glu198, Thr292, and Gly225, aided by hydrophobic interactions involving the rest of the molecule. These results suggest a relationship between the antibacterial activity shown mainly with the 4-thioxopyrimidine portion, leading to the investigation of new compounds that use this scaffold.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Modelos Moleculares
/
Conformação Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Mol Model
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Alemanha