Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents
Copyright © 2020 Elsevier Inc. All rights reserved..
The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26-3.90 µM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 µM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
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| Enthalten in: |
Bioorganic chemistry - 105(2020) vom: 03. Dez., Seite 104383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ahadi, Hamideh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.06.2021 Date Revised 16.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2020.104383 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316987921 |
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| 245 | 1 | 0 | |a Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents |
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| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26-3.90 µM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 µM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 1,3,4-Thiadiazole | |
| 650 | 4 | |a Anticancer activity | |
| 650 | 4 | |a Apoptosis inducer | |
| 650 | 4 | |a Ciprofloxacin | |
| 650 | 4 | |a Cytotoxicity | |
| 650 | 4 | |a Fluoroquinolones | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Thiadiazoles |2 NLM | |
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| 650 | 7 | |a Ciprofloxacin |2 NLM | |
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| 700 | 1 | |a Shokrzadeh, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Hosseini-Khah, Zahra |e verfasserin |4 aut | |
| 700 | 1 | |a Ghassemi Barghi, Nasrin |e verfasserin |4 aut | |
| 700 | 1 | |a Ghasemian, Majid |e verfasserin |4 aut | |
| 700 | 1 | |a Emadi, Elnaz |e verfasserin |4 aut | |
| 700 | 1 | |a Zargari, Mehryar |e verfasserin |4 aut | |
| 700 | 1 | |a Razzaghi-Asl, Nima |e verfasserin |4 aut | |
| 700 | 1 | |a Emami, Saeed |e verfasserin |4 aut | |
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