Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1), pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6-bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized ligands and silver(I) complexes were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes exhibited better activity than the ligands, and the results have been compared with doxorubicin as a reference drug. 1. Introduction Chemical and biological activity of the organic complexes is not possessed only by the metal or organic ligand but also this activity can be fine-tuned by subtle changes in the electronic and steric properties of the complexes or by variation of the oxidation state of the metal. These features provide a versatile platform for drug design that is now being exploited in several areas. For centuries, silver compounds have been known to possess interesting biological properties that show potent antibacterial properties [1–4]. Also, they were popular remedies for tetanus and rheumatism in the 19th century and for colds and gonorrhea before the advent of antibiotics in the early part of the 20th century [5]. Additionally, silver compounds used for treating mental illness, epilepsy, and nicotine addiction [6, 7]. Furthermore, silver compounds have reemerged as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers [8–11]. On the other hand, functionalized pyridine derivatives are gaining a great deal of interest in medicinal and organic synthesis, where some of pyridine derivatives are used as bactericides [12], fungicides [13], and anticancer agents [14–17]. In view of these observations and in continuation of our current interest in the synthesis of organic compounds for biological evaluations [18–25] and our interest in the chemistry of 2,6-disubstituted pyridine derivatives [26–29], we described herein a facile synthesis of novel silver complex with some of the newly synthesized 2,6-disubstituted pyridine ligands. The newly synthesized compounds were evaluated for their in vitro anticancer activity against four human cancer cell lines including hepatocellular carcinoma (HePG2), lung adenocarcinoma
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