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Updated: Dec 2, 2025
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics
Raimundo de A M Neto1, Cleydson B R Santos1, Shayanne V C Henriques1
1Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá, Brasil.
Abstract:
Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation.Communicated by Ramaswamy H. Sarma.
Insights
Synthetic chalcones show significant antineoplastic activity against glioblastoma (GBM) cancer cells. Molecular modeling suggests interaction with tubulin, indicating potential for new glioblastoma drug development.
Area of Science:
- Oncology
- Medicinal Chemistry
- Molecular Biology
Background:
- Glioblastoma (GBM) is an aggressive central nervous system (CNS) tumor with poor patient survival rates.
- Development of novel therapeutic agents for GBM remains a critical unmet need.
- Existing treatments for glioblastoma have limited efficacy, highlighting the need for new drug candidates.
Purpose of the Study:
- To evaluate the antineoplastic activity of synthetic chalcones (compounds 3a-3f) against glioblastoma.
- To investigate the molecular interactions of these chalcones with potential targets using molecular modeling.
- To assess the potential of chalcones as novel therapeutic agents for glioblastoma.
Main Methods:
- In vitro cytotoxicity assays using glioblastoma cell lines (AHOL1, U87) and healthy fibroblasts (AN27).
- Molecular docking studies to predict binding interactions with target proteins.
- Molecular dynamics simulations to assess the stability and conformational behavior of chalcone-tubulin complexes.
Main Results:
- Synthetic chalcones significantly reduced the viability of glioblastoma cell lines (AHOL1, U87) compared to healthy fibroblasts (AN27).
- Molecular docking revealed interactions with serine and LYS352 amino acids, suggesting a role in inhibiting cell growth and interaction with tubulin.
- Molecular dynamics confirmed the stability of chalcone-tubulin interactions, similar to the control doxorubicin.
Conclusions:
- Synthetic chalcones exhibit significant antineoplastic potential against glioblastoma.
- Interaction with tubulin, particularly involving LYS352, is a likely mechanism for their cytotoxic effect.
- Further studies are warranted to fully elucidate the mechanism of action and therapeutic potential of these chalcones in glioblastoma treatment.
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