Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
OBJECTIVE: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage.
METHODS: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay.
RESULTS: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3.
CONCLUSION: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Medicinal chemistry (Shariqah (United Arab Emirates)) - 16(2020), 3 vom: 29., Seite 340-349 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moghadam, Ebrahim S [VerfasserIn] |
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| Links: |
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| Themen: |
Acetamides |
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| Anmerkungen: |
Date Completed 18.11.2020 Date Revised 18.11.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1573406415666190425153717 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM296526746 |
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| 100 | 1 | |a Moghadam, Ebrahim S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide |
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| 500 | |a Date Revised 18.11.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a OBJECTIVE: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage | ||
| 520 | |a METHODS: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay | ||
| 520 | |a RESULTS: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3 | ||
| 520 | |a CONCLUSION: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Caspases 3/7 | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a indibulin | |
| 650 | 4 | |a pyrrole | |
| 650 | 4 | |a synthesis | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Pyrroles |2 NLM | |
| 650 | 7 | |a Tubulin Modulators |2 NLM | |
| 700 | 1 | |a Saravani, Farhad |e verfasserin |4 aut | |
| 700 | 1 | |a Hamel, Ernest |e verfasserin |4 aut | |
| 700 | 1 | |a Shahsavari, Zahra |e verfasserin |4 aut | |
| 700 | 1 | |a Alipour, Mohsen |e verfasserin |4 aut | |
| 700 | 1 | |a Hosseinkhani, Saman |e verfasserin |4 aut | |
| 700 | 1 | |a Ostad, Seyednasser |e verfasserin |4 aut | |
| 700 | 1 | |a Amini, Mohsen |e verfasserin |4 aut | |
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