In Vitro Anti-tumoral and Anti-bacterial Activity of an Octamolybdate Cluster-Based Hybrid Solid Incorporated with a Copper Picolinate Complex.

Abstract

Inorganic drugs, especially polyoxometalate-based hybrids, are expected to be developed as promising future metallodrugs. Herein, an organic-inorganic hybrid solid based on pyridine-2-carboxylic acid or picolinic acid (pic), [(Cu(pic)2)2(Mo8O26)]·8H2O (1), was synthesized. A single-crystal structure of a solid possesses a discrete β-type octamolybdate cluster that supramolecularly aggregates with a {Cu2(pic)4}4- complex and eight lattice water molecules. The study indicates that the solid is stable in aqueous medium and less toxic toward normal cell lines. The in vitro anti-bacterial and anti-tumor properties of the solid 1 were investigated. The results of the anti-tumor action against various human cancer cell lines, namely, lung (A549), breast (MCF-7), and liver (HepG2) cancer cells suggest that this β-octamolybdate-based solid yielded the lowest IC50 value reported so far among octamolybdate anion-based hybrid solids, i.e., 24.24 μM for MCF-7, 21.56 μM for HepG2, and 25 μM for A549, indicating significant anti-cancer activity. The cell cycle analysis further reveals the observed anti-tumor effect to be governed by the arrest of breast cancer cells in the G2/M phase while that of lung and liver cancer cells in the S phase of the cell cycle. A fluorescence quenching study suggests the binding interaction between solid and ctDNA, which in turn induces apoptosis and necrosis pathways leading to cancer cell death. This is also the first study of {Mo8O26}4- cluster-based solids as an anti-bacterial agent against Escherichia coli, and it was found to be very effective with a minimal inhibitory concentration value of ∼135 μg/mL, which is the lowest so far reported for any octamolybdate-based solid.