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Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives

Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyros...

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Autores principales: Zargaham, Muhammad Kazim, Ahmed, Madiha, Akhtar, Nosheen, Ashraf, Zaman, Abdel-Maksoud, Mostafa A., Aufy, Mohammed, Nadeem, Humaira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303221/
https://www.ncbi.nlm.nih.gov/pubmed/37375782
http://dx.doi.org/10.3390/ph16060835
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author Zargaham, Muhammad Kazim
Ahmed, Madiha
Akhtar, Nosheen
Ashraf, Zaman
Abdel-Maksoud, Mostafa A.
Aufy, Mohammed
Nadeem, Humaira
author_facet Zargaham, Muhammad Kazim
Ahmed, Madiha
Akhtar, Nosheen
Ashraf, Zaman
Abdel-Maksoud, Mostafa A.
Aufy, Mohammed
Nadeem, Humaira
author_sort Zargaham, Muhammad Kazim
collection PubMed
description Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC(50) value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC(50) = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein–ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be −8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors.
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spelling pubmed-103032212023-06-29 Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives Zargaham, Muhammad Kazim Ahmed, Madiha Akhtar, Nosheen Ashraf, Zaman Abdel-Maksoud, Mostafa A. Aufy, Mohammed Nadeem, Humaira Pharmaceuticals (Basel) Article Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC(50) value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC(50) = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein–ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be −8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors. MDPI 2023-06-02 /pmc/articles/PMC10303221/ /pubmed/37375782 http://dx.doi.org/10.3390/ph16060835 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
Zargaham, Muhammad Kazim
Ahmed, Madiha
Akhtar, Nosheen
Ashraf, Zaman
Abdel-Maksoud, Mostafa A.
Aufy, Mohammed
Nadeem, Humaira
Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title_full Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title_fullStr Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title_full_unstemmed Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title_short Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives
title_sort synthesis, in silico studies, and antioxidant and tyrosinase inhibitory potential of 2-(substituted phenyl) thiazolidine-4-carboxamide derivatives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303221/
https://www.ncbi.nlm.nih.gov/pubmed/37375782
http://dx.doi.org/10.3390/ph16060835
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