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Volume 21, Issue 17
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Despite advancements in treatment modalities, the search for new cytotoxic agents remains vital in the fight against cancer. This ongoing effort aims to introduce novel molecules that serve as potent cytotoxic agents while minimizing adverse effects.

Objective

The objective of the study is to design, synthesize, and evaluate Fmoc-L-Lysine Carboxamides for cytotoxic activities.

Methods

The title compounds were synthesized by esterification followed by reduction of Fmoc-Lys (Boc)-OH to alcohol, then coupled with various aryl/alkyl/alicyclic carboxylic acids. These compounds were then analysed using 13C NMR, 1H NMR, FT-IR, and Mass spectroscopic techniques and evaluated for cytotoxic activity by MTT assay, apoptosis induction, cell cycle analysis, EGFR-TK inhibition activity, molecular docking, and molecular dynamics simulation studies.

Results

The results obtained by MTT assay indicated that compounds and demonstrated significant cytotoxicity against A549 and SKOV3 cell lines, with IC values of 2.75 and 1.91μM compared to doxorubicin. Further, the analysis of the Cell cycle and apoptosis proposed that arrested the cell cycle in the G0/G1 phase, whereas arrested the cell cycle in the G2/M phase and triggered apoptosis in cancer cells. Notably, compound demonstrated the highest inhibition of EGFR with IC, 0.189μM, and acted as its potential inhibitor. Molecular docking and dynamics simulation studies further confirmed the stability of in the active site of EGFR.

Conclusion

Overall, these results suggested that the synthesized derivatives offer a promising approach for the advancement of new and effective cancer therapies.

© 2024 Bentham Science Publishers
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2024-10-03
2025-04-06

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Design, Synthesis, Biological Evaluation, Molecular Docking, and Molecular Dynamics Simulation Studies of Fmoc-L-Lysine Carboxamides as Promising Cytotoxic Agents
Letters in Drug Design & Discovery 21, 4057 (2024); https://doi.org/10.2174/0115701808324766240930062735
/content/journals/lddd/10.2174/0115701808324766240930062735
/content/journals/lddd/10.2174/0115701808324766240930062735
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  • Article Type:     Research Article
Keyword(s): Anticancer; cytotoxic; docking; EGFR; lysine; molecular dynamics

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