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Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity
Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049166/ https://www.ncbi.nlm.nih.gov/pubmed/36982181 http://dx.doi.org/10.3390/ijms24065101 |
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author | Efremov, Alexander M. Beznos, Olga V. Eremeev, Roman O. Chesnokova, Natalia B. Milaeva, Elena R. Shevtsova, Elena F. Lozinskaya, Natalia A. |
author_facet | Efremov, Alexander M. Beznos, Olga V. Eremeev, Roman O. Chesnokova, Natalia B. Milaeva, Elena R. Shevtsova, Elena F. Lozinskaya, Natalia A. |
author_sort | Efremov, Alexander M. |
collection | PubMed |
description | Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5–10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr). |
format | Online Article Text |
id | pubmed-10049166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100491662023-03-29 Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity Efremov, Alexander M. Beznos, Olga V. Eremeev, Roman O. Chesnokova, Natalia B. Milaeva, Elena R. Shevtsova, Elena F. Lozinskaya, Natalia A. Int J Mol Sci Article Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5–10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr). MDPI 2023-03-07 /pmc/articles/PMC10049166/ /pubmed/36982181 http://dx.doi.org/10.3390/ijms24065101 Text en © 2023 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 Efremov, Alexander M. Beznos, Olga V. Eremeev, Roman O. Chesnokova, Natalia B. Milaeva, Elena R. Shevtsova, Elena F. Lozinskaya, Natalia A. Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title | Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title_full | Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title_fullStr | Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title_full_unstemmed | Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title_short | Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity |
title_sort | microwave-assisted synthesis of 3-hydroxy-2-oxindoles and pilot evaluation of their antiglaucomic activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049166/ https://www.ncbi.nlm.nih.gov/pubmed/36982181 http://dx.doi.org/10.3390/ijms24065101 |
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