Synthesis of indole-substituted thiosemicarbazones as an aldose reductase inhibitor : an in vitro, selectivity and in silico study
Aim: Indole is an important component of many drug molecules, and its conjugation with thiosemicarbazone moiety would be advantageous in finding lead compounds for the development of diabetic complications. Methodology: We have designed, synthesized and evaluated a series of 17 indole-thiosemicarbazones (3a-q) as aldose reductase (ALR2) and aldehyde reductase (ALR1) inhibitors. Results: After in vitro evaluation, all indole-thiosemicarbazones showed significant inhibition against both enzyme ALR1 and ALR2 with IC50 in range of 0.42-20.7 and 1.02-19.1 μM, respectively. The docking study was also carried out to consider the putative binding of molecules with the target enzymes. Conclusion: Compound 3f was found to be most active and selective for ALR2. The indole-thiosemicarbazones series described here has selective hits for diabetes-mellitus-associated complications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Future medicinal chemistry - 13(2021), 14 vom: 20. Juli, Seite 1185-1201 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shehzad, Muhammad Tariq [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.10.2021 Date Revised 22.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2020-0060 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326958363 |
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| 100 | 1 | |a Shehzad, Muhammad Tariq |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis of indole-substituted thiosemicarbazones as an aldose reductase inhibitor |b an in vitro, selectivity and in silico study |
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| 500 | |a Date Completed 22.10.2021 | ||
| 500 | |a Date Revised 22.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Indole is an important component of many drug molecules, and its conjugation with thiosemicarbazone moiety would be advantageous in finding lead compounds for the development of diabetic complications. Methodology: We have designed, synthesized and evaluated a series of 17 indole-thiosemicarbazones (3a-q) as aldose reductase (ALR2) and aldehyde reductase (ALR1) inhibitors. Results: After in vitro evaluation, all indole-thiosemicarbazones showed significant inhibition against both enzyme ALR1 and ALR2 with IC50 in range of 0.42-20.7 and 1.02-19.1 μM, respectively. The docking study was also carried out to consider the putative binding of molecules with the target enzymes. Conclusion: Compound 3f was found to be most active and selective for ALR2. The indole-thiosemicarbazones series described here has selective hits for diabetes-mellitus-associated complications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a aldehyde reductase | |
| 650 | 4 | |a aldose reductase | |
| 650 | 4 | |a antidiabetic agent | |
| 650 | 4 | |a indole | |
| 650 | 4 | |a sorbinil | |
| 650 | 4 | |a thiosemicarbazone | |
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| 650 | 7 | |a Imidazolidines |2 NLM | |
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| 700 | 1 | |a Khan, Ajmal |e verfasserin |4 aut | |
| 700 | 1 | |a Halim, Sobia Ahsan |e verfasserin |4 aut | |
| 700 | 1 | |a Hameed, Abdul |e verfasserin |4 aut | |
| 700 | 1 | |a Imran, Aqeel |e verfasserin |4 aut | |
| 700 | 1 | |a Iqbal, Jamshed |e verfasserin |4 aut | |
| 700 | 1 | |a Ullah, Aziz |e verfasserin |4 aut | |
| 700 | 1 | |a Asari, Asnuzilawati |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Samra |e verfasserin |4 aut | |
| 700 | 1 | |a Shafiq, Zahid |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Harrasi, Ahmed |e verfasserin |4 aut | |
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