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

In this work, novel ‘2 + 1’ mixed ligand tricarbonyl Re I complexes of the general type fac -[Re(CO) 3 (NN)X] 0/+ , where NN is a diimine ligand bearing the anticancer scaffold of 2-(4′-aminophenyl)benzothiazole, and X is Br − ( 1 ), Η 2 Ο ( 2 ), pyridine ( 3 ), cyclohexyl isocyanide ( 4 ), triphenylphosphine ( 5 ) and 1,3,5-triaza-7-phosphaadamantane ( 6 ), were synthesized, characterized, and evaluated. This design uses rhenium and phenylbenzothiazole to generate targeted, multipotent metal-based anticancer agents with tunable pharmacokinetics. Except for compound 6 , all complexes exhibited IC 50 values ranging from 0.19 to 6.28 μM against HeLa (ovarian), MCF-7 (breast), and A431 (epidermoid) cancer cell lines, outperforming cisplatin under the same conditions, while showing evidence of synergistic action between the pharmacophore and the rhenium core. In addition, their interaction with calf thymus DNA was investigated, with the data indicating intercalation. Complex 4 , with the most potent anticancer activity, was additionally labeled with 99m Tc and exhibited optimal stability and high lipophilicity. Its in vivo biodistribution was studied in healthy and SCID mice bearing MCF-7 xenografts, showing good tumor uptake and retention. Finally, a detailed X-ray crystallographic study of molecular packing revealed a plethora of intermolecular interactions, including hydrogen bonds, π-π overlap, and carbonyl···carbonyl interactions. The high anticancer potency and tumor-targeting properties make these compounds promising anticancer agents.