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

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>), 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 i...

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Autores principales: Mara Gutiérrez-Sánchez, Aurelio Romero-Castro, José Correa-Basurto, Martha Cecilia Rosales-Hernández, Itzia Irene Padilla-Martínez, Jessica Elena Mendieta-Wejebe
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spelling oai:doaj.org-article:a964201dc07d49c3a8486aaa6196e02a2021-11-25T18:27:21ZPreclinical 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 Activity10.3390/molecules262268011420-3049https://doaj.org/article/a964201dc07d49c3a8486aaa6196e02a2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6801https://doaj.org/toc/1420-3049Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>), 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 <b>C1</b> 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, <b>C1</b> belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for <b>C1</b> 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 <b>C1</b> (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, <b>C1</b> 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.Mara Gutiérrez-SánchezAurelio Romero-CastroJosé Correa-BasurtoMartha Cecilia Rosales-HernándezItzia Irene Padilla-MartínezJessica Elena Mendieta-WejebeMDPI AGarticle5-5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>)aminosalicylic acidRP-HPLCpharmacokineticsulcerative colitisCrohn’s diseaseOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6801, p 6801 (2021)
institution DOAJ
collection DOAJ
language EN
topic 5-5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>)
aminosalicylic acid
RP-HPLC
pharmacokinetics
ulcerative colitis
Crohn’s disease
Organic chemistry
QD241-441
spellingShingle 5-5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>)
aminosalicylic acid
RP-HPLC
pharmacokinetics
ulcerative colitis
Crohn’s disease
Organic chemistry
QD241-441
Mara Gutiérrez-Sánchez
Aurelio Romero-Castro
José Correa-Basurto
Martha Cecilia Rosales-Hernández
Itzia Irene Padilla-Martínez
Jessica Elena Mendieta-Wejebe
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
description Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (<b>C1</b>), 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 <b>C1</b> 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, <b>C1</b> belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for <b>C1</b> 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 <b>C1</b> (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, <b>C1</b> 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.
format article
author Mara Gutiérrez-Sánchez
Aurelio Romero-Castro
José Correa-Basurto
Martha Cecilia Rosales-Hernández
Itzia Irene Padilla-Martínez
Jessica Elena Mendieta-Wejebe
author_facet Mara Gutiérrez-Sánchez
Aurelio Romero-Castro
José Correa-Basurto
Martha Cecilia Rosales-Hernández
Itzia Irene Padilla-Martínez
Jessica Elena Mendieta-Wejebe
author_sort Mara Gutiérrez-Sánchez
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a964201dc07d49c3a8486aaa6196e02a
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