Synthesis of Four Steroidal Carbamates with Antitumor Activity against Mouse Colon Carcinoma CT26WT Cells: In Vitro and In Silico Evidence
| Autor: | Daylin Fernández Pacheco, Dayana Alonso, Leonardo González Ceballos, Armando Zaldo Castro, Sheila Brown Roldán, Mairelys García Díaz, Anabel Villa Testa, Sarah Fuentes Wagner, Janet Piloto-Ferrer, Yamilet Coll García, Andrés F. Olea, Luis Espinoza |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Molecular Structure
Organic Chemistry Carcinoma Antineoplastic Agents General Medicine synthesis steroidal carbamates colorectal cancer molecular docking Catalysis Computer Science Applications Inorganic Chemistry Molecular Docking Simulation Mice Structure-Activity Relationship Cell Line Tumor Colonic Neoplasms Animals Humans Steroids Carbamates Physical and Theoretical Chemistry Drug Screening Assays Antitumor Molecular Biology Spectroscopy Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8775 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158775 |
| Popis: | Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results. |
| Databáze: | OpenAIRE |
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