Synthesis and in Vitro Cytotoxicity Evaluation of Phenanthrene Linked 2,4- Thiazolidinediones as Potential Anticancer Agents
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Updated: Dec 14, 2025
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Upasana Yadav1, Yogesh Vanjari1, Kritika Laxmikeshav1
1Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Objective:
To synthesize a series of phenanthrene-thiazolidinedione hybrids and explore their cytotoxic potential against human cancer cell lines of A-549 (lung cancer), HCT-116 and HT-29 (colon cancer), MDA MB-231 (triple-negative breast cancer), BT-474 (breast cancer) and (mouse melanoma) B16F10 cells.
Methods:
A new series of phenanthrene-thiazolidinedione hybrids was synthesized via Knoevenagel condensation of phenanthrene-9-carbaldehyde and N-alkylated thiazolidinediones. The cytotoxicity (IC50) of the synthesized compounds was determined by MTT assay. Apoptotic assays like (AO/EB) and DAPI staining, cell cycle analysis, JC-1 staining and Annexin V binding assay studies were performed for the most active compound (Z)- 3-(4-bromobenzyl)-5-((2,3,6,7-tetramethoxyphenanthren-9-yl)methylene)thiazolidine-2,4-dione (17b). Molecular docking, dynamics and evaluation of pharmacokinetic (ADME/T) properties were also carried out by using Schrödinger.
Results And Discussion:
From the series of tested compounds, 17b unveiled promising cytotoxic action with an IC50 value of 0.985±0.02μM on HCT-116 human colon cancer cells. The treatment of HCT-116 cells with 17b demonstrated distinctive apoptotic morphology like shrinkage of cells, horseshoe-shaped nuclei formation and chromatin condensation. The flow-cytometry analysis revealed the G0/G1 phase cell cycle arrest in a dosedependent fashion. The AO/EB, DAPI, DCFDA, Annexin-V and JC-1 staining studies were performed in order to determine the effect of the compound on cell viability. Computational studies were performed by using Schrödinger to determine the stability of the ligand with the DNA.
Conclusion:
The current study provides an insight into developing a series of phenanthrene thiazolidinedione derivatives as potential DNA interactive agents which might aid in colon cancer therapy.
Insights
This study synthesized novel phenanthrene-thiazolidinedione hybrids and found compound 17b to be highly effective against colon cancer cells. This research offers potential new treatments for colon cancer by developing DNA-interactive agents.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Computational Chemistry
Background:
- Phenanthrene and thiazolidinedione scaffolds are known for their biological activities.
- Developing novel anticancer agents is crucial for combating drug resistance and improving patient outcomes.
Purpose of the Study:
- To synthesize and characterize new phenanthrene-thiazolidinedione hybrids.
- To evaluate the cytotoxic potential of these hybrids against various human cancer cell lines.
- To investigate the mechanism of action of the most potent compound, including its effect on apoptosis and cell cycle progression.
Main Methods:
- Synthesis of phenanthrene-thiazolidinedione hybrids via Knoevenagel condensation.
- Cytotoxicity assessment using MTT assay.
- Apoptosis and cell cycle analysis via AO/EB staining, DAPI staining, flow cytometry, JC-1 staining, and Annexin V binding assay.
- Computational studies including molecular docking, dynamics, and ADME/T prediction using Schrödinger.
Main Results:
- Compound 17b exhibited significant cytotoxic activity against HCT-116 colon cancer cells (IC50 = 0.985 ± 0.02 μM).
- Treatment with 17b induced apoptosis and G0/G1 phase cell cycle arrest in HCT-116 cells.
- Computational studies suggested potential DNA interaction and favorable pharmacokinetic properties for compound 17b.
Conclusions:
- Phenanthrene-thiazolidinedione hybrids represent a promising class of compounds for cancer therapy.
- Compound 17b demonstrates potential as a DNA-interactive agent for colon cancer treatment.
- Further investigation into these derivatives could lead to the development of novel anticancer drugs.
