Benzothiazole diimine rhenium(I) '2 + 1' complexes: Synthesis, structural characterization and anticancer activity.

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Development of novel metal-based anticancer agents is crucial for overcoming limitations of existing therapies.
• Rhenium (Re) complexes offer unique electronic and coordination properties for drug design.
• The 2-(4'-aminophenyl)benzothiazole scaffold is recognized for its anticancer potential.

Purpose of the Study:

• To synthesize and characterize novel mixed ligand tricarbonyl Re(I) complexes incorporating the 2-(4'-aminophenyl)benzothiazole anticancer scaffold.
• To evaluate the in vitro anticancer activity of these complexes against various human cancer cell lines.
• To investigate the mechanism of action, including DNA interaction and in vivo biodistribution of promising candidates.

Main Methods:

• Synthesis and characterization of six novel fac-[Re(CO)3(NN)X] complexes (X = Br-, H2O, pyridine, cyclohexyl isocyanide, triphenylphosphine, 1,3,5-triaza-7-phosphaadamantane).
• In vitro cytotoxicity assays (IC50 values) against HeLa, MCF-7, and A431 cancer cell lines.
• DNA binding studies (intercalation), 99mTc radiolabeling, lipophilicity assessment, in vivo biodistribution studies in mice, and X-ray crystallography.

Main Results:

• Five of the six synthesized complexes displayed significant anticancer activity (IC50 values 0.19–6.28 μM), outperforming cisplatin.
• Evidence of synergistic action between the rhenium core and the benzothiazole pharmacophore was observed.
• Complex 4 showed potent activity, good stability, high lipophilicity, and favorable in vivo tumor uptake and retention.

Conclusions:

• The novel rhenium complexes demonstrate high anticancer potency and tumor-targeting properties, positioning them as promising anticancer drug candidates.
• The design strategy effectively combines rhenium and the benzothiazole scaffold for multipotent, targeted therapy.
• Further investigation into these rhenium complexes is warranted for their potential clinical application.