Design, synthesis and mechanistic study of new dual targeting HDAC/tubulin inhibitors
Aim: The purpose of this work is to create and synthesize a new class of chemicals: 3-cyano-2-substituted pyridine compounds with expected multitarget inhibition of histone deacetylase (HDAC) and tubulin. Materials & methods: The target compounds (3a-c, 4a-c and 5a-c) were synthesized utilizing 6-(4-methoxyphenyl)-2-oxo-4-(3,4,5-trimethoxyphenyl)-3-cyanopyridine, with various linkers and zinc-binding groups (ZBGs). Results: Most of the tested compounds showed promising growth inhibition, and hydroxamic acid-containing hybrids possessed higher HDAC inhibition than other ZBGs. Compound 4b possessed the highest potency; however, it showed the most tubulin polymerization inhibition. Docking studies displayed good binding into HDAC1 and six pockets and tubulin polymerization protein. Conclusion: Compound 4b could be considered a good antitumor candidate to go further into in vivo and clinical studies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Future medicinal chemistry - 16(2024), 7 vom: 13. März, Seite 601-622 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
El-Zoghbi, Mona S [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0336 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36925984X |
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| 245 | 1 | 0 | |a Design, synthesis and mechanistic study of new dual targeting HDAC/tubulin inhibitors |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: The purpose of this work is to create and synthesize a new class of chemicals: 3-cyano-2-substituted pyridine compounds with expected multitarget inhibition of histone deacetylase (HDAC) and tubulin. Materials & methods: The target compounds (3a-c, 4a-c and 5a-c) were synthesized utilizing 6-(4-methoxyphenyl)-2-oxo-4-(3,4,5-trimethoxyphenyl)-3-cyanopyridine, with various linkers and zinc-binding groups (ZBGs). Results: Most of the tested compounds showed promising growth inhibition, and hydroxamic acid-containing hybrids possessed higher HDAC inhibition than other ZBGs. Compound 4b possessed the highest potency; however, it showed the most tubulin polymerization inhibition. Docking studies displayed good binding into HDAC1 and six pockets and tubulin polymerization protein. Conclusion: Compound 4b could be considered a good antitumor candidate to go further into in vivo and clinical studies | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a A Abuo-Rahma, Gamal El-Din |e verfasserin |4 aut | |
| 700 | 1 | |a Mohamed, Mamdouh Fa |e verfasserin |4 aut | |
| 700 | 1 | |a Badr, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Ghulikah, Hanan A |e verfasserin |4 aut | |
| 700 | 1 | |a Abdelhafez, El-Shimaa Mn |e verfasserin |4 aut | |
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