Design and synthesis of 1,4-benzothiazine derivatives with promising effects against colorectal cancer cells
| Autor: | Amit Rai, Dinesh Kumar, Amit K Keshari, Sudipta Saha, Ashok K. Singh, Vinit Raj, Umesh Kumar |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Colorectal cancer Stereochemistry Benzothiazine 01 natural sciences lcsh:Chemistry 03 medical and health sciences Molecular dynamics chemistry.chemical_compound HT-29 cells DOCK medicine Molecule Computational analysis lcsh:Science 010405 organic chemistry General Engineering medicine.disease Combinatorial chemistry 0104 chemical sciences molecular docking and dynamics 030104 developmental biology interleukins chemistry colon cancer caspases lcsh:QD1-999 Docking (molecular) Molecular targets lcsh:Q 1 4-benzothiazine |
| Zdroj: | Cogent Chemistry, Vol 3, Iss 1 (2017) |
| DOI: | 10.6084/m9.figshare.4807636.v2 |
| Popis: | In this study, we designed and synthesized a series of 1,4-benzothiazine and evaluated them for anticancer activity toward HT-29 human colon cancer cells using SRB assay. Before the synthesis, docking studies were performed using various molecular targets of colon cancer including IL-2, IL-6, COX-2, caspase-3, and caspase-8. The molecular dynamic (MD) simulation was also executed to examine the stability of ligand-receptor complex of more stable dock conformation. Further computational study was carried out in order to predict the pharmacokinetic profile of titled compounds. Among 34 tested compounds, compounds AR13 and AR15 were found to be active against HT-29 cells (GI50 . Moreover, Compounds AR5, AR22, and AR34 showed the moderate activity with GI50 −5 kcal/mol for AR13 and AR15 with all the molecular targets and the ligand-protein complex was found stable after its formation. Again, computational analysis revealed that both molecules AR13 and AR15 had good ADMET profiling. These encouraging outcomes allowed us to conclude that both AR13 and AR15 may emerge as lead compounds against colon cancer. |
| Databáze: | OpenAIRE |
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