Selective Binding Profiles of Curcumin Derivatives to G-Quadruplex (G4) Structures Found in Human Oncogene Promoters

Abstract

G-Quadruplex (G4) structures are special significant DNA topologies formed by accumulation of G-tetrads which are planar structures of four guanine residues interacting with hydrogen bonds through Hoogsten edges around monovalent cations such as potassium (K) or sodium (Na). While these special topologies are mostly observed in telomere regions, they might be found over regulatory regions of the genes such as promoter, enhancer etc. In addition, since that various oncogenes carry G4 structures over their promoters, it’s highlighted that G4s have significant role over cancer prognosis through regulation of expression level. To date, binding profiles of curcumin having great antioxidant and anti-inflammatory properties and its derivatives to G4s found in telomere regions and promoter of c-Myc were discovered. As such, to discover selective binding profiles of curcumin derivatives to G4s found in promoters of various oncogenes such as c-Myc, c-KIT, hTERT, RET, VEGF, and PARP1 have quite potential in the drug design for several cancer types. In light of these information, 18 curcumin derivatives from ZINC15 database were docked to related G4 structures. ADME and toxicity properties of all derivatives were analyzed and biological reactivity as well as molecular electrostatic surface potential (MESP) features of totally 4 derivatives (C11, C13, C14, and C15) exhibiting selective binding pattern to certain G4s were analyzed with density functional theory (DFT) method.