Exploration of newly synthesized amantadine-thiourea conjugates for their DNA binding, anti-elastase, and anti-glioma potentials
Copyright © 2024 Elsevier B.V. All rights reserved..
Three newly synthesized amantadine thiourea conjugates namely MS-1 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)benzamide, MS-2 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)-4-methylbenzamide and MS-3 N-((3 s,5 s,7 s)-adamantan-1-ylcarbamothioyl)-4-chlorobenzamide were investigated for their structures, bindings (DNA/ elastase), and for their impact on healthy and cancerous cells. Theoretical (DFT/docking) and experimental {UV-visible (UV-), fluorescence (Flu-), and cyclic voltammetry (CV)} studies indicated binding interactions of each conjugate with DNA and elastase enzyme. Theoretically and experimentally calculated binding parameters for conjugate - DNA interaction revealed MS-3 - DNA to have most significant binding with comparatively greater values of binding parameters {(Kb/M-1: docking, 3.8 × 105; UV-, 5.95 × 103; Flu-,1.55 × 105; CV, 1.52 × 104), (∆G/ kJmol-1: docking, -32.09; UV-, -22.40; Flu-,-30.81; CV, -24.82)}. The docked structures, greater bindings site size values (n), and the trend in DNA viscosity changes in the presence of each conjugate concentration confirmed a mixed binding mode of interaction among them. Conjugate - elastase binding by docking agreed with the experimental anti-elastase findings. Cytotoxicity studies of each tested conjugate demonstrated greater cytotoxicity for cancerous (MG-U87) cells in comparison to control, while for the normal (HEK-293) cells the cytotoxicity was found comparatively low. Overall exploration suggested that MS-3 is the most effective candidate for DNA binding, anti-elastase, and for anti-glioma activities.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:263 |
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| Enthalten in: |
International journal of biological macromolecules - 263(2024), Pt 1 vom: 25. März, Seite 130231 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arshad, Nasima [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2024.130231 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368590461 |
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| 100 | 1 | |a Arshad, Nasima |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exploration of newly synthesized amantadine-thiourea conjugates for their DNA binding, anti-elastase, and anti-glioma potentials |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 27.03.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Three newly synthesized amantadine thiourea conjugates namely MS-1 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)benzamide, MS-2 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)-4-methylbenzamide and MS-3 N-((3 s,5 s,7 s)-adamantan-1-ylcarbamothioyl)-4-chlorobenzamide were investigated for their structures, bindings (DNA/ elastase), and for their impact on healthy and cancerous cells. Theoretical (DFT/docking) and experimental {UV-visible (UV-), fluorescence (Flu-), and cyclic voltammetry (CV)} studies indicated binding interactions of each conjugate with DNA and elastase enzyme. Theoretically and experimentally calculated binding parameters for conjugate - DNA interaction revealed MS-3 - DNA to have most significant binding with comparatively greater values of binding parameters {(Kb/M-1: docking, 3.8 × 105; UV-, 5.95 × 103; Flu-,1.55 × 105; CV, 1.52 × 104), (∆G/ kJmol-1: docking, -32.09; UV-, -22.40; Flu-,-30.81; CV, -24.82)}. The docked structures, greater bindings site size values (n), and the trend in DNA viscosity changes in the presence of each conjugate concentration confirmed a mixed binding mode of interaction among them. Conjugate - elastase binding by docking agreed with the experimental anti-elastase findings. Cytotoxicity studies of each tested conjugate demonstrated greater cytotoxicity for cancerous (MG-U87) cells in comparison to control, while for the normal (HEK-293) cells the cytotoxicity was found comparatively low. Overall exploration suggested that MS-3 is the most effective candidate for DNA binding, anti-elastase, and for anti-glioma activities | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amantadine-thiourea conjugates | |
| 650 | 4 | |a Anti-elastase activity | |
| 650 | 4 | |a Cytotoxicity for normal & cancerous cells | |
| 650 | 4 | |a DFT/docking | |
| 650 | 4 | |a Spectroscopic/electrochemical DNA binding | |
| 650 | 7 | |a Thiourea |2 NLM | |
| 650 | 7 | |a GYV9AM2QAG |2 NLM | |
| 650 | 7 | |a Amantadine |2 NLM | |
| 650 | 7 | |a BF4C9Z1J53 |2 NLM | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 650 | 7 | |a Pancreatic Elastase |2 NLM | |
| 650 | 7 | |a EC 3.4.21.36 |2 NLM | |
| 700 | 1 | |a Shakeel, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Javed, Aneela |e verfasserin |4 aut | |
| 700 | 1 | |a Perveen, Fouzia |e verfasserin |4 aut | |
| 700 | 1 | |a Saeed, Aamer |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Atteeque |e verfasserin |4 aut | |
| 700 | 1 | |a Ismail, Hammad |e verfasserin |4 aut | |
| 700 | 1 | |a Channar, Pervaiz Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Naseer, Fatima |e verfasserin |4 aut | |
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