Study on the Structural Variability and Antiproliferative Activity of Fe (II) Compounds Based on Different Substituents of 4′‐Phenyl‐2,2′:6′,2′′‐Terpyridines

The family of Fe (II) complexes ( 1 – 8 ) bearing 4′‐(substituted‐phenyl)‐2,2′:6′,2′′‐terpyridine ligands were prepared and characterized, in which the para‐position of the phenyl is substituted by hydrogen (L 1 ), methyl (L 2 ), F (L 3 ), Cl (L 4 ), I (L 5 ), methoxy (L 6 ), carboxyl (L 7 ), and methylsulfonyl (L 8 ). Compounds 2 , 4 , and 6 are dinuclear structures bridged by one water molecule, while the other five compounds are mononuclear. Compounds in vitro antiproliferative activity and cytotoxicity were evaluated against three human carcinoma cell lines: Eca‐109 (esophageal squamous carcinoma), Bel‐7402 (hepatocellular carcinoma), SiHa (cervical squamous carcinoma) and the normal HL‐7702 hepatocyte line. The results demonstrate that the complexes exhibit superior antiproliferative activity against cancer cells compared to cisplatin, while showing significantly lower cytotoxicity toward normal cells. Among them, 3 (F‐substituted) displayed the lowest IC 50 values against Eca‐109 and Bel‐7402, whereas 2 (methyl‐substituted) showed the highest potency against SiHa. UV‐vis and circular dichroism (CD) spectroscopic studies revealed intercalative binding between the complexes and DNA, a mechanism further corroborated by molecular modeling. These findings highlight the potential of complexes 1 – 8 as promising candidates for chemotherapeutic agents targeting human tumors, warranting further preclinical investigation.