Quimque, Mark Tristan J. and Mandigma, Mark John P. and Lim, Justin Allen K. and Budde, Simon and Dahse, Hans-Martin and Villaflores, Oliver B. and Hallare, Arnold and Macabeo, Allan Patrick G. (2020) Synthesis, Characterization, and Molecular Docking Studies of N-Acylated Butyro and Valerolactam Derivatives with Antiproliferative and Cytotoxic Activities. LETTERS IN DRUG DESIGN & DISCOVERY, 17 (6). pp. 725-730. ISSN 1570-1808, 1875-628X
Full text not available from this repository. (Request a copy)Abstract
Background: Electrophilic compounds bearing Michael acceptors present great promise in anticancer drug discovery. Methods: Drawing inspirations from cytotoxic Piper lactam alkaloids, twelve N-acylated butyro- and valerolactams were prepared and evaluated for antiproliferative and cytotoxic activities against the normal human umbilical vein endothelial cells (HUVEC), chronic human myeloid leukemia cells (K-5 62), and Henrietta Lacks (HeLa) cells used as model cell lines. Molecular docking of bioactive derivatives was performed against tyrosine kinase. Results: Results of the MTT assay showed the crotonylated (5) and nitro-containing cinnamoyl (8) butyrolactams, and, the crotonylated (10), trifluoromethylated (13), and chlorinated (14) cinnamoyl valerolactam derivatives as the most antiproliferative against human myeloid leukemia cells. The trifluoromethylated cinnamoyl valerolactam (13) displayed the best selectivity on K-562 cells. Molecular docking studies of 13 against tyrosine kinase provided evidence as tyrosine kinase inhibitor, having comparable binding energy and receptor interaction with imatinib. Conclusion: The presence of electrophilic N- acrylic moieties contributes to the potential of a compound as inspiration to develop anti-leukemia drugs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Lactams; antiproliferative; cytotoxic; tyrosine kinase; molecular docking; (HeLa) cells; human umbilical vein endothelial cells (HUVEC) |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2021 11:31 |
| Last Modified: | 09 Apr 2021 11:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45471 |
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