A series of aminosugar-conjugated Schiff base complexes for anticancer therapy

• Main Authors: Alba, Laurenzo De Vera, Hatanaka, Tsubasa, Nakai, Misaki, Yano, Shigenobu, Yajima, Tatsuo, Nomoto, Akihiro, Funahashi, Yasuhiro
• Format: text
• Published: Animo Repository 2019
• Subjects: Amino sugars; Schiff bases; Cancer—Treatment
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11266
• Institution: De La Salle University

Currently, platinum compounds are being used as the mainstay for many anticancer therapies despite the dose-limiting side effects, so there is a need to search for better candidate drugs having similar mechanism of action. Recently, palladium and platinum complexes 1 and 2 of a Schiff base ligand “Oqn”, composed of an aminosugar (such as glucosamine) and 8-hydroxy-2- quinolinecarboxaldehyde, were developed and show promising anticancer effectiveness, even against cisplatin-resistant cancer cell lines. Intracellular signal protein targeting by 1 and DNA strand breaks caused by 2 have been proposed as the mechanism for anticancer activity. In an effort to improve stability and to study the mechanism of action, we have also synthesized the galactosamine (3, 4) and the acetylated glucosamine analogs (5, 6, 7) of the abovementioned complexes. Interaction of the non-acetylated complexes 1, 2, 3, and 4 with bovine serum albumin were carried out by fluorescence-quenching assay and circular dichroism spectroscopy. When the glucosamine- containing Oqn complexes are dissolved in water, hydrolysis of the complex occurs rather rapidly. We have studied the rate of hydrolysis of complexes 1 and 2 in different aqueous solutions and determined the influence of pH and chloride concentration. Finally, we have synthesized possible hydrolysis products of the Pt- and Pd-Oqn (GlcN) complexes; both were characterized by X-ray crystallography and the hydrolysis product of Pd-Oqn (GlcN) was confirmed by 1 H NMR. We propose the mechanisms by which the hydrolysis occurs based on these findings.