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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
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.
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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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