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Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics
A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N(2)H(4) to get aromatic sulfonyl hydrazides 2(a-d). The intermediate hydrazides 2(a-d) were treated w...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054763/ https://www.ncbi.nlm.nih.gov/pubmed/32149140 http://dx.doi.org/10.1155/2020/8104107 |
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author | Abas, Mujahid Rafique, Hummera Shamas, Shazia Roshan, Sadia Ashraf, Zaman Iqbal, Zafar Raza, Hussain Hassan, Mubashir Afzal, Khurram Rizvanov, Albert A. Asad, Muhammad Hassham Hassan Bin |
author_facet | Abas, Mujahid Rafique, Hummera Shamas, Shazia Roshan, Sadia Ashraf, Zaman Iqbal, Zafar Raza, Hussain Hassan, Mubashir Afzal, Khurram Rizvanov, Albert A. Asad, Muhammad Hassham Hassan Bin |
author_sort | Abas, Mujahid |
collection | PubMed |
description | A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N(2)H(4) to get aromatic sulfonyl hydrazides 2(a-d). The intermediate hydrazides 2(a-d) were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases 3(a-j). The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of 3(a-j) on carbonic anhydrase activity were determined, and it was found that derivative 3c exhibited the most potent activity with IC(50)0.84 ± 0.12 μM among all other derivatives and is also more active than standard acetazolamide (IC(50)0.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound 3c inhibits the enzyme by noncompetitive mode of inhibition with K(i) value 8.6 μM. The molecular docking investigations of the synthesized analogues 3(a-j) were evaluated which assured that synthesized compounds bind well inside the active binding site of the target enzyme. Cytotoxicity on human keratinocyte (HaCaT) and MCF-7 cell lines was performed, and it was found that most of the synthesized analogues were nontoxic on these cell lines and the toxic effects follow the dose-dependent manner. Based on our investigations, it was suggested that analogue 3c may serve as core structure to project carbonic anhydrase inhibitors with greater potency. |
format | Online Article Text |
id | pubmed-7054763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-70547632020-03-08 Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics Abas, Mujahid Rafique, Hummera Shamas, Shazia Roshan, Sadia Ashraf, Zaman Iqbal, Zafar Raza, Hussain Hassan, Mubashir Afzal, Khurram Rizvanov, Albert A. Asad, Muhammad Hassham Hassan Bin Biomed Res Int Research Article A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N(2)H(4) to get aromatic sulfonyl hydrazides 2(a-d). The intermediate hydrazides 2(a-d) were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases 3(a-j). The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of 3(a-j) on carbonic anhydrase activity were determined, and it was found that derivative 3c exhibited the most potent activity with IC(50)0.84 ± 0.12 μM among all other derivatives and is also more active than standard acetazolamide (IC(50)0.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound 3c inhibits the enzyme by noncompetitive mode of inhibition with K(i) value 8.6 μM. The molecular docking investigations of the synthesized analogues 3(a-j) were evaluated which assured that synthesized compounds bind well inside the active binding site of the target enzyme. Cytotoxicity on human keratinocyte (HaCaT) and MCF-7 cell lines was performed, and it was found that most of the synthesized analogues were nontoxic on these cell lines and the toxic effects follow the dose-dependent manner. Based on our investigations, it was suggested that analogue 3c may serve as core structure to project carbonic anhydrase inhibitors with greater potency. Hindawi 2020-02-20 /pmc/articles/PMC7054763/ /pubmed/32149140 http://dx.doi.org/10.1155/2020/8104107 Text en Copyright © 2020 Mujahid Abas et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Abas, Mujahid Rafique, Hummera Shamas, Shazia Roshan, Sadia Ashraf, Zaman Iqbal, Zafar Raza, Hussain Hassan, Mubashir Afzal, Khurram Rizvanov, Albert A. Asad, Muhammad Hassham Hassan Bin Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title | Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title_full | Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title_fullStr | Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title_full_unstemmed | Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title_short | Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics |
title_sort | sulfonamide-based azaheterocyclic schiff base derivatives as potential carbonic anhydrase inhibitors: synthesis, cytotoxicity, and enzyme inhibitory kinetics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054763/ https://www.ncbi.nlm.nih.gov/pubmed/32149140 http://dx.doi.org/10.1155/2020/8104107 |
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