DNA G-quadruplexes binding and antitumor activity of palladium awl oxime ligand complexes encapsulated in either albumin or algal cellulose nanoparticles

摘要

The interactions between two Pd complexes, designated as [Pd-3(C,N-(C6H4C(Cl) = NO)-4)(6)] (complex 1) and [Pd-3(C12H8C = NO)(6)] (complex 2), with the human telomeric G-quadruplex DNA, 5 '-G(3)(T(2)AG(3))(3)-3' (HTG21), were monitored using spectroscopic, biological, and molecular modeling studies. According to the UV-vis results, these complexes can strongly induce and stabilize G-quadruplex DNA structure with K-b1 = 4.5(+/- 0.3) x 10(6) M-1 and K-b2 = 1.0(+/- 0.2) x 10(7) M-1 via groove mode in comparison with duplex DNA. The release mechanism of the Pd complexes from BSA nanoparticles followed a biphasic pattern unlike that of algal cellulose nanoparticles in vitro. In addition, the cytotoxicity of these complexes on MCF-7 cancer cells and PBMC normal cells was evaluated and compared with cisplatin under similar experimental conditions. Furthermore, to determine and verify the interaction mode of these compounds with G-quadruplex, the molecular docking technique was also performed. Our data clearly demonstrated that complex 2 had higher activity and cytotoxicity than that of complex 1 and could be further investigated in the future as a drug discovery platform.