Hologram quantitative structure-activity relationship and comparative molecular interaction field analysis of aminothiazole and thiazolesulfonamide as reversible LSD1 inhibitors.
Future Med Chem
; 7(11): 1381-94, 2015.
Article
em En
| MEDLINE
| ID: mdl-26230878
ABSTRACT
BACKGROUND:
LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inhibition decreases cellular proliferation and therefore represents a therapeutic target for cancer treatment. MAO and LSD-1 are both flavin adenine dinucleotide-dependent MAOs, and the MAO inhibitor, tranylcypromine, is currently undergoing clinical trials for cancer treatment because it acts as an irreversible LSD-1 inhibitor. MATERIALS &METHODS:
The present study investigated new reversible LSD-1 inhibitors, in order to develop novel selective anticancer agents. We constructed 2 and 3D quantitative structure-activity relationship models by using a series of 54 aminothiazole and thiazolesulfonamide derivatives.RESULTS:
The models were validated internally and externally (q(2) , 0.691 and 0.701; r(2) , 0.894 and 0.937; r(2) test , 0.785 and 0.644, for 2 and 3D models, respectively). Fragment contribution maps, as well as steric and electrostatic contour maps were generated in order to obtain chemical information related to LSD-1 inhibition.CONCLUSION:
The thiazolesulfonamide group was fundamental to the inhibition of LSD-1 by these compounds and that bulky and aromatic substituents at the thiazole ring were important for their steric and electrostatic interactions with the active site of LSD-1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Tiazóis
/
Inibidores Enzimáticos
/
Histona Desmetilases
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Brasil