Synthesis, Characterization, and Molecular Docking Studies of N-Acylated Butyro and Valerolactam Derivatives with Antiproliferative and Cytotoxic Activities

Author(s): Mark Tristan J. Quimque, Mark John P. Mandigma, Justin Allen K. Lim, Simon Budde, Hans-Martin Dahse, Oliver B. Villaflores, Arnold V. Hallare, Allan Patrick G. Macabeo*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 6 , 2020

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Graphical 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- 562), 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.

Keywords: Lactams, antiproliferative, cytotoxic, tyrosine kinase, molecular docking, (HeLa) cells, human umbilical vein endothelial cells (HUVEC).

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Article Details

Year: 2020
Page: [725 - 730]
Pages: 6
DOI: 10.2174/1570180816666190716141524
Price: $65

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