Dual functional dinuclear platinum complex with selective reactivity towards c-myc G-quadruplex

• Main Authors: He, Lei, Meng, Zhenyu, Xu, Dechen, Shao, Fangwei
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2018
• Subjects: G-quadruplexes (GQ); Dinuclear Platinum Complexes
• Online Access: https://hdl.handle.net/10356/87503; http://hdl.handle.net/10220/45427
• Institution: Nanyang Technological University

G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising targets for developing anticancer therapeutic molecules. However, the current drug development mainly focused on non-covalent dynamic binders to stabilize GQ structures, while the covalent targeting from inorganic complexes via chelating principles, as a potent therapeutic strategy was surprisingly lack of exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(μ-diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain two dual-functional Pt cores connected by an alkyl linkage. Pt3 with nonanediamine linkage optimized the specific binding towards c-myc G-quadruplex via dual functional clamp on GQ as 1) non-covalently π-stacking of aromatic ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3′- and 5′-ends.