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1,5-Benzothiazepine Derivatives: Green Synthesis, In Silico and In Vitro Evaluation as Anticancer Agents
| Content Provider | MDPI |
|---|---|
| Author | Haroun, Michelyne Chobe, Santosh S. Alavala, Rajasekhar Reddy Mathure, Savita M. Jamullamudi, Risy Namratha Nerkar, Charushila K. Gugulothu, Vijay Kumar Tratrat, Christophe Islam, Mohammed Monirul Venugopala, Katharigatta N. Habeebuddin, Mohammed Telsang, Mallikarjun Sreeharsha, Nagaraja Anwer, Khalid |
| Copyright Year | 2022 |
| Description | Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol-400 (PEG-400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG-400. PEG-400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a–2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase-3β, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G-2, with an $IC_{50}$ of 3.29 ± 0.15 µM, whereas the standard drug $IC_{50}$ was 4.68 ± 0.17 µM. In the prostate cancer cell line DU-145, the compounds displayed $IC_{50}$ ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an $IC_{50}$ of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives. |
| Starting Page | 3757 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules27123757 |
| Journal | Molecules |
| Issue Number | 12 |
| Volume Number | 27 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-06-10 |
| Access Restriction | Open |
| Subject Keyword | Molecules Medicinal Chemistry 1,5-benzothiazepines Peg-400 Molecular Docking Cytotoxicity Anticancer |
| Content Type | Text |
| Resource Type | Article |
