Effects of 1,4-dihydropyridine derivatives on cell injury and mTOR of HepG2 and 3D-QSAR study.
Comput Biol Chem
; 109: 108010, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38232515
ABSTRACT
1,4-dihydropyridine derivatives (1,4-DHPs) are a class of drugs used to treat cardiovascular diseases, but these drugs can cause liver injury. To reveal the toxicity characteristics of these compounds, we used a series of assays, including cell viability, enzyme activity detection, and western blotting, to investigate the toxicity of seven kinds of 1,4-DHPs (0-100⯵M) on HepG2 cells and establish 3D-QSAR model based on relevant toxicity data. After HepG2 cells were treated with 1,4-DHPs for 24â¯h, high-dose (100⯵M) 1,4-DHPs decreased cell viability to varying degrees, while ROS and MDA contents were significantly increased, and ATP content was reduced. Moreover, with the concentration of 100⯵M 1,4-DHPs (Nimodipine, Nitrendipine, Cilnidipine, and Manidipine) were markedly inhibited the phosphorylation levels of mTOR protein. The results of the 3D-QSAR model showed that the non-cross validation coefficient (R2) and cross validation coefficient (Q2) of the model were 0.982 and 0.652, respectively. Combined with external validation and the Williams diagram, the model showed good predictability and application domain. Based on the CoMSIA 3D contour map, the introduction of large volume and hydrogen bond receptor groups on the carbonyl oxygen side chains of the 1,4-DHPs ring 3- and 5- was beneficial for reducing the toxicity of 1,4-DHPs. The results of this study could supplement information on the cytotoxicity of 1,4-DHPs, and could provide theoretical support for predicting the toxicity of 1,4-DHPs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Dihidropiridinas
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Bloqueadores de los Canales de Calcio
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Relación Estructura-Actividad Cuantitativa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Comput Biol Chem
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China