Quinolyl‐Based PGM Metallarectangles: Antiproliferative Activity, DNA and BSA Protein Interactions, and a Molecular Docking Perspective

The increased success of small metal‐containing molecules as pharmaceutical agents has prompted investigations into the pharmacological activity of a different class of metal‐based compounds; supramolecular coordination complexes (SCCs). Such complexes have been extensively investigated for their anticancer activity, with many displaying activities comparable or superior to available clinical chemotherapeutic drugs. Here, we evaluated a series of quinoline‐containing binuclear complexes and metallarectangles for their in vitro anticancer activity in the hormone receptor positive MCF‐7 and triple negative MDA‐MB‐231 breast cancer cell lines. The preliminary cytotoxic screen, in the MCF‐7 cell line, revealed that the ligand (7‐chloro‐4‐(pyridin‐4‐yl)quinoline, L) and metallarectangle [{Ir(μ‐Cl)(Cp*)}4(μ‐L)2](OTf)4 display superior activity to cisplatin, while [{Ru(p‐cymene)}4(μ‐η2‐η2‐C2O4)2(μ‐L)2](OTf)4 was more potent than cisplatin in the triple‐negative MDA‐MD‐231 cell line. Upon evaluation in a multidose screen, ligand L and metallarectangle [{Ir(μ‐Cl)(Cp*)}4(μ‐L)2](OTf)4 displayed antiproliferative activity almost two‐fold greater than cisplatin in the MCF‐7 cell line, while [{Ru(p‐cymene)}4(μ‐η2‐η2‐C2O4)2(μ‐L)2](OTf)4 was over two‐times more active than cisplatin in the MDA‐MB‐231 cell line. Additionally, using the non‐tumorigenic MCF‐12 A breast epithelial cell line, the compounds demonstrate increased selectivity toward breast cancer cells over non‐tumorigenic cells. Furthermore, investigations into the interactions of ligand L and selected complexes with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA) indicate favourable binding. From a different angle: We explored the incorporation of a quinolyl motif, ubiquitous to antimalarial chemotherapy, as part of PGM metallarectangles, intending to gain insight into the anticancer properties exemplified by this structure.