Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity

Gutiérrez-Sánchez, Mara; Romero-Castro, Aurelio; Correa-Basurto, José; Rosales-Hernández, Martha Cecilia; Padilla-Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

doi:10.3390/molecules26226801

Open AccessArticle

Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity

by

Mara Gutiérrez-Sánchez

¹

,

Aurelio Romero-Castro

^2,*,

José Correa-Basurto

³

,

Martha Cecilia Rosales-Hernández

¹

,

Itzia Irene Padilla-Martínez

⁴

and

Jessica Elena Mendieta-Wejebe

^1,*

¹

Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón S/N, Colonia Casco de Santo Tomas, Ciudad de Mexico 11340, Mexico

²

División de Ciencias de la Salud, Universidad de Quintana Roo, Av. Erick Paolo Martínez S/N, esquina Av. 4 de marzo, Colonia Magisterial, Chetumal 77039, Mexico

³

Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón S/N, Colonia Casco de Santo Tomas, Ciudad de Mexico 11340, Mexico

⁴

Laboratorio de Química Supramolecular y Nanociencias, Departamento de Ciencias Básicas, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Av. Acueducto S/N, Colonia Barrio La Laguna Ticomán, Ciudad de Mexico 07340, Mexico

^*

Authors to whom correspondence should be addressed.

Molecules 2021, 26(22), 6801; https://doi.org/10.3390/molecules26226801

Submission received: 30 September 2021 / Revised: 1 November 2021 / Accepted: 2 November 2021 / Published: 11 November 2021

(This article belongs to the Special Issue Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives)

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Abstract

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease.

Keywords: 5-5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1); aminosalicylic acid; RP-HPLC; pharmacokinetics; ulcerative colitis; Crohn’s disease

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MDPI and ACS Style

Gutiérrez-Sánchez, M.; Romero-Castro, A.; Correa-Basurto, J.; Rosales-Hernández, M.C.; Padilla-Martínez, I.I.; Mendieta-Wejebe, J.E. Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity. Molecules 2021, 26, 6801. https://doi.org/10.3390/molecules26226801

AMA Style

Gutiérrez-Sánchez M, Romero-Castro A, Correa-Basurto J, Rosales-Hernández MC, Padilla-Martínez II, Mendieta-Wejebe JE. Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity. Molecules. 2021; 26(22):6801. https://doi.org/10.3390/molecules26226801

Chicago/Turabian Style

Gutiérrez-Sánchez, Mara, Aurelio Romero-Castro, José Correa-Basurto, Martha Cecilia Rosales-Hernández, Itzia Irene Padilla-Martínez, and Jessica Elena Mendieta-Wejebe. 2021. "Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity" Molecules 26, no. 22: 6801. https://doi.org/10.3390/molecules26226801

APA Style

Gutiérrez-Sánchez, M., Romero-Castro, A., Correa-Basurto, J., Rosales-Hernández, M. C., Padilla-Martínez, I. I., & Mendieta-Wejebe, J. E. (2021). Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity. Molecules, 26(22), 6801. https://doi.org/10.3390/molecules26226801

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Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity

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