Background: Thiosemicarbazone (TSC) is a Schiff base that has been receiving considerable attention
owing to its promising biological implication and remarkable pharmacological properties. The most promising drug
candidate of this class would be Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) which has entered
phase II clinical trials as a potent anti-cancer chemotherapeutic agent.
Objective: The current research aimed to synthesize several Schiff base ligands from (3-formyl-4-hydroxyphenyl)
methyltriphenylphosphonium (T). Additionally, the current research aimed to study the growth inhibitory effect of
triphenylphosphonium containing thiosemicarbazone derivatives on PC-3 cells by deciphering the mechanisms
involved in cell death.
Method: The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR,
HRESIMS and X-ray crystallography) and the results were in conformity with the structure of the targeted compounds.
Growth inhibitory effect of the compounds were performed against six human cell lines.
Results: DM(tsc)T displayed most potent activity against PC-3 cells with IC50 value of 2.64 ± 0.33 μM, surpassing
that of the positive control cisplatin (5.47 ± 0.06 μM). There were marked morphological changes observed in
DM(tsc)T treated cells stained with acridine orange and ethidium bromide which were indicative of cell apoptosis.
Treatment with DM(tsc)T showed that the cell cycle is arrested in the G0/G1 phase after 72 hours. Mitochondrial
membrane potential loss was observed in cells treated with DM(tsc)T, indicating the apoptosis could be due to
mitochondria mediated pathway.
Conclusion: This study indicates that DM(tsc)T would serve as a lead scaffold for rational anticancer agent development.