TY - JOUR
T1 - In Combo Studies for the Optimization of 5-Aminoanthranilic Acid Derivatives as Potential Multitarget Drugs for the Management of Metabolic Syndrome
AU - Chávez-Gutiérrez, Edwin
AU - Martínez-Arellanes, Matilda
AU - Murillo-López, Montserrat
AU - Medina-Guzmán, María Fernanda
AU - Mobarak-Richaud, Laila
AU - Pelcastre-Guzmán, Karen
AU - Quintana-Romero, Osvaldo Javier
AU - Ariza-Castolo, Armando
AU - Ayala-Moreno, María del Rosario
AU - Salazar, Juan Rodrigo
AU - Guerra-Araiza, Christian
AU - Rodríguez-Páez, Lorena
AU - Pinto-Almazán, Rodolfo
AU - Loza-Mejía, Marco A.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/12
Y1 - 2022/12
N2 - Metabolic syndrome is a set of risk factors that consist of abdominal obesity, arterial hypertension, alterations in the lipid profile, and hyperglycemia. The current therapeutic strategy includes polypharmacy, using three or more drugs to control each syndrome component. However, this approach has drawbacks that could lead to therapeutic failure. Multitarget drugs are molecules with the ability to act on different targets simultaneously and are an attractive alternative for treating complex diseases such as metabolic syndrome. Previously, we identified a triamide derivative of 5-aminoanthranilic acid that exhibited hypoglycemic, hypolipemic, and antihypertensive activities simultaneously. In the present study, we report the synthesis and in combo evaluation of new derivatives of anthranilic acid, intending to identify the primary structural factors that improve the activity over metabolic syndrome-related parameters. We found that substitution on position 5, incorporation of 3,4-dimethoxyphenyl substituents, and having a free carboxylic acid group lead to the in vitro inhibition of HMG-CoA reductase, and simultaneously the diminution of the serum levels of glucose, triglycerides, and cholesterol in a diet-induced in vivo model.
AB - Metabolic syndrome is a set of risk factors that consist of abdominal obesity, arterial hypertension, alterations in the lipid profile, and hyperglycemia. The current therapeutic strategy includes polypharmacy, using three or more drugs to control each syndrome component. However, this approach has drawbacks that could lead to therapeutic failure. Multitarget drugs are molecules with the ability to act on different targets simultaneously and are an attractive alternative for treating complex diseases such as metabolic syndrome. Previously, we identified a triamide derivative of 5-aminoanthranilic acid that exhibited hypoglycemic, hypolipemic, and antihypertensive activities simultaneously. In the present study, we report the synthesis and in combo evaluation of new derivatives of anthranilic acid, intending to identify the primary structural factors that improve the activity over metabolic syndrome-related parameters. We found that substitution on position 5, incorporation of 3,4-dimethoxyphenyl substituents, and having a free carboxylic acid group lead to the in vitro inhibition of HMG-CoA reductase, and simultaneously the diminution of the serum levels of glucose, triglycerides, and cholesterol in a diet-induced in vivo model.
KW - anthranilic acid
KW - metabolic syndrome
KW - molecular docking
KW - multitarget drugs
UR - http://www.scopus.com/inward/record.url?scp=85144737080&partnerID=8YFLogxK
U2 - 10.3390/ph15121461
DO - 10.3390/ph15121461
M3 - Artículo
C2 - 36558912
AN - SCOPUS:85144737080
SN - 1424-8247
VL - 15
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 12
M1 - 1461
ER -