Antiproliferative, apoptosis-inducing activity and molecular docking studies of sydnones compounds
Objective: To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies.
Material and Methods: Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server.
Result: In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 μM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study.
Conclusion: The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Journal of cancer research and therapeutics - 18(2022), 3 vom: 15. Apr., Seite 681-690 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hossain, Syed Lidia [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 01.08.2022 Date Revised 01.08.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.4103/jcrt.JCRT_1614_20 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332471608 |
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| 100 | 1 | |a Hossain, Syed Lidia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antiproliferative, apoptosis-inducing activity and molecular docking studies of sydnones compounds |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 01.08.2022 | ||
| 500 | |a Date Revised 01.08.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Objective: To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies | ||
| 520 | |a Material and Methods: Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server | ||
| 520 | |a Result: In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 μM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study | ||
| 520 | |a Conclusion: The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Sydnones | |
| 650 | 4 | |a apoptosis | |
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| 700 | 1 | |a Mathews, Manoj |e verfasserin |4 aut | |
| 700 | 1 | |a Bhyranalyar Nagarajappa, Veerabhadra Swamy |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, B Kiran |e verfasserin |4 aut | |
| 700 | 1 | |a Veerappa Yelamaggad, Channabasa Veshwar |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, C Rajendra |e verfasserin |4 aut | |
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