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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis, Assessment of Antineoplastic Activity, and Molecular Docking of Novel 2-Thioxo-oxazolidin-4-one Derivatives

Author(s): Eduardo Augusto Vasconcelos de Freitas Ramalho*, Douglas Carvalho Francisco Viana, Valécia de Cassia Mendonça da Costa, Maira Pitta, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta and Marina Galdino da Rocha Pitta

Volume 18, Issue 9, 2022

Published on: 29 April, 2022

Page: [980 - 989] Pages: 10

DOI: 10.2174/1573406418666220304221557

Price: $65

Abstract

Background: Oxazolidinones display several biological effects, including anticancer activity. The purpose of this present work was to investigate a series of novel oxazolidinone derivatives with potential antineoplastic activity. Their mechanisms of death induction and effects in the cell cycle were also evaluated. A molecular docking study was accomplished through proteins of the Cyclin-Dependent Kinases family (CDK). The new compound LPSF/NBM-2 was appeared to promote cell cycle arrest at the G2/M phase and increase the percentage of apoptotic cells.

Methods: Oxazolidinone derivatives were obtained through Knoevenagel condensation. The cytotoxic assay was evaluated through the MTT method. Moreover, flow cytometry was performed in order to investigate the effects of the new compounds on the cell cycle, induction of cell death, and apoptosis. A blind docking was performed through the SwissDock online server and the analysis of the results was performed using the UCSF Chimera and Biovia discovery studio software.

Results: LPSF/NBM-1 and LPSF/NBM-2 displayed the most cytotoxic activity against HL-60 (IC50 = 54.83 μM) and MOLT-4 (IC50 = 51.61 μM) cell lines. LPSF/NBM-2 showed an increased percentage of cell population at the G2/M phase. Molecular-docking results of LPSF/NBM-1 and LPSF/NBM-2 suggested a binding affinity with the evaluated CDK proteins.

Conclusion: LPSF/NBM-1 and LPSF/NBM-2 displayed cytotoxic profiles against Hl-60 and MOLT-4. LPSF/NBM-2 increased cell population percentage at the G2/M phase and promoted cell death compared to non-treated cells in the MOLT-4 cell line. Based on these findings, oxazolidinone derivatives could be highlighted as possible cytostatic agents against lymphoma cells. Molecular docking results suggested the action of LPSF/NBM-1 and LPSF/NBM-2 compounds on enzymes of cyclin-dependent kinases family, however, more studies are needed to establish this correlation.

Keywords: Oxazolidinone, anticancer activity, cell death, cell cycle arrest, antineoplastic, apoptosis, CDK.

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