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
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.