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Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine
Dapsone (DpS) is an antimicrobial and antiprotozoal agent, especially used to treat leprosy. The drug shares a similar mode of action with sulfonamides. Additionally, it possesses anti-inflammatory activity, useful for treating autoimmune diseases. Here, we developed a “me-better” alternative to sul...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949065/ https://www.ncbi.nlm.nih.gov/pubmed/35336057 http://dx.doi.org/10.3390/pharmaceutics14030684 |
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author | Kang, Changyu Kim, Jaejeong Ju, Sanghyun Park, Sohee Yoo, Jin-Wook Yoon, In-Soo Kim, Min-Soo Jung, Yunjin |
author_facet | Kang, Changyu Kim, Jaejeong Ju, Sanghyun Park, Sohee Yoo, Jin-Wook Yoon, In-Soo Kim, Min-Soo Jung, Yunjin |
author_sort | Kang, Changyu |
collection | PubMed |
description | Dapsone (DpS) is an antimicrobial and antiprotozoal agent, especially used to treat leprosy. The drug shares a similar mode of action with sulfonamides. Additionally, it possesses anti-inflammatory activity, useful for treating autoimmune diseases. Here, we developed a “me-better” alternative to sulfasalazine (SSZ), a colon-specific prodrug of mesalazine (5-ASA) used as an anti-inflammatory bowel diseases drug; DpS azo-linked with two molecules of 5-ASA (AS-DpS-AS) was designed and synthesized, and its colon specificity and anti-colitic activity were evaluated. AS-DpS-AS was converted to DpS and the two molecules of 5-ASA (up to approximately 87% conversion) within 24 h after incubation in the cecal contents. Compared to SSZ, AS-DpS-AS showed greater efficiency in colonic drug delivery following oral gavage. Simultaneously, AS-DpS-AS substantially limited the systemic absorption of DpS. In a dinitrobenzene sulfonic acid-induced rat colitis model, oral AS-DpS-AS elicited better efficacy against rat colitis than oral SSZ. Moreover, intracolonic treatment with DpS and/or 5-ASA clearly showed that combined treatment with DpS and 5-ASA was more effective against rat colitis than the single treatment with either DpS or 5-ASA. These results suggest that AS-DpS-AS may be a “me-better” drug of SSZ with higher therapeutic efficacy, owing to the combined anti-colitic effects of 5-ASA and DpS. |
format | Online Article Text |
id | pubmed-8949065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89490652022-03-26 Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine Kang, Changyu Kim, Jaejeong Ju, Sanghyun Park, Sohee Yoo, Jin-Wook Yoon, In-Soo Kim, Min-Soo Jung, Yunjin Pharmaceutics Article Dapsone (DpS) is an antimicrobial and antiprotozoal agent, especially used to treat leprosy. The drug shares a similar mode of action with sulfonamides. Additionally, it possesses anti-inflammatory activity, useful for treating autoimmune diseases. Here, we developed a “me-better” alternative to sulfasalazine (SSZ), a colon-specific prodrug of mesalazine (5-ASA) used as an anti-inflammatory bowel diseases drug; DpS azo-linked with two molecules of 5-ASA (AS-DpS-AS) was designed and synthesized, and its colon specificity and anti-colitic activity were evaluated. AS-DpS-AS was converted to DpS and the two molecules of 5-ASA (up to approximately 87% conversion) within 24 h after incubation in the cecal contents. Compared to SSZ, AS-DpS-AS showed greater efficiency in colonic drug delivery following oral gavage. Simultaneously, AS-DpS-AS substantially limited the systemic absorption of DpS. In a dinitrobenzene sulfonic acid-induced rat colitis model, oral AS-DpS-AS elicited better efficacy against rat colitis than oral SSZ. Moreover, intracolonic treatment with DpS and/or 5-ASA clearly showed that combined treatment with DpS and 5-ASA was more effective against rat colitis than the single treatment with either DpS or 5-ASA. These results suggest that AS-DpS-AS may be a “me-better” drug of SSZ with higher therapeutic efficacy, owing to the combined anti-colitic effects of 5-ASA and DpS. MDPI 2022-03-21 /pmc/articles/PMC8949065/ /pubmed/35336057 http://dx.doi.org/10.3390/pharmaceutics14030684 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kang, Changyu Kim, Jaejeong Ju, Sanghyun Park, Sohee Yoo, Jin-Wook Yoon, In-Soo Kim, Min-Soo Jung, Yunjin Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title | Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title_full | Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title_fullStr | Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title_full_unstemmed | Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title_short | Dapsone Azo-Linked with Two Mesalazine Moieties Is a “Me-Better” Alternative to Sulfasalazine |
title_sort | dapsone azo-linked with two mesalazine moieties is a “me-better” alternative to sulfasalazine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949065/ https://www.ncbi.nlm.nih.gov/pubmed/35336057 http://dx.doi.org/10.3390/pharmaceutics14030684 |
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