Synthesis of 3-hydroxy-2-naphthohydrazide-based hydrazones and their implications in diabetic management via in vitro and in silico approaches
© 2023 Deutsche Pharmazeutische Gesellschaft..
Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:357 |
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| Enthalten in: |
Archiv der Pharmazie - 357(2024), 2 vom: 27. Feb., Seite e2300544 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tasleem, Mussarat [VerfasserIn] |
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| Links: |
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| Themen: |
α-glucosidase |
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| Anmerkungen: |
Date Completed 05.02.2024 Date Revised 05.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ardp.202300544 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Halim, Sobia Ahsan |e verfasserin |4 aut | |
| 700 | 1 | |a Urooj, Ifra |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Nadeem |e verfasserin |4 aut | |
| 700 | 1 | |a Munir, Rabia |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Ajmal |e verfasserin |4 aut | |
| 700 | 1 | |a El-Kott, Attalla F |e verfasserin |4 aut | |
| 700 | 1 | |a Taslimi, Parham |e verfasserin |4 aut | |
| 700 | 1 | |a Negm, Sally |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Harrasi, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Shafiq, Zahid |e verfasserin |4 aut | |
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