Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization
AIM: Discovery of novel series of colchicine binding site inhibitors (CBSIs).
MATERIALS & METHODS: Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI.
CONCLUSION: Compounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Future medicinal chemistry - 10(2018), 16 vom: 01. Aug., Seite 1907-1924 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moussa, Shaimaa A [VerfasserIn] |
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| Links: |
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| Themen: |
5-(4-chlorophenyl)furan |
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| Anmerkungen: |
Date Completed 20.05.2019 Date Revised 25.02.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2018-0036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM286094932 |
|---|
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| 100 | 1 | |a Moussa, Shaimaa A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.05.2019 | ||
| 500 | |a Date Revised 25.02.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a AIM: Discovery of novel series of colchicine binding site inhibitors (CBSIs) | ||
| 520 | |a MATERIALS & METHODS: Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI | ||
| 520 | |a CONCLUSION: Compounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a 5-(4-chlorophenyl)furan | |
| 650 | 4 | |a colchicine | |
| 650 | 4 | |a tubulin | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Furans |2 NLM | |
| 650 | 7 | |a Tubulin |2 NLM | |
| 650 | 7 | |a Tubulin Modulators |2 NLM | |
| 650 | 7 | |a Colchicine |2 NLM | |
| 650 | 7 | |a SML2Y3J35T |2 NLM | |
| 700 | 1 | |a A Osman, Essam Eldin |e verfasserin |4 aut | |
| 700 | 1 | |a Eid, Nahed M |e verfasserin |4 aut | |
| 700 | 1 | |a Abou-Seri, Sahar M |e verfasserin |4 aut | |
| 700 | 1 | |a El Moghazy, Samir M |e verfasserin |4 aut | |
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