In Combo Studies for the Optimization of 5-Aminoanthranilic Acid Derivatives as Potential Multitarget Drugs for the Management of Metabolic Syndrome

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...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-11, Vol.15 (12), p.1461
Main Authors: Chávez-Gutiérrez, Edwin, Martínez-Arellanes, Matilda, Murillo-López, Montserrat, Medina-Guzmán, María Fernanda, Mobarak-Richaud, Laila, Pelcastre-Guzmán, Karen, Quintana-Romero, Osvaldo Javier, Ariza-Castolo, Armando, Ayala-Moreno, María Del Rosario, Salazar, Juan Rodrigo, Guerra-Araiza, Christian, Rodríguez-Páez, Lorena, Pinto-Almazán, Rodolfo, Loza-Mejía, Marco A
Format: Article
Language:English
Subjects:
Acids
anthranilic acid
Antilipemic agents
Cholesterol
Diagnosis
Diet
Disease
Dosage and administration
Drug therapy
Glucose
Ligands
Metabolic diseases
Metabolic disorders
Metabolic syndrome
molecular docking
Mortality
multitarget drugs
Polypharmacy
Structure
Testing
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Summary: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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15121461