Guanidino-Aryl Derivatives: Binding to DNA, RNA and G-Quadruplex Structure and Antimetabolic Activity
Year: 2025
Type: article
Abstract: A series of novel guanidino-aryl (GA) compounds containing phenanthrene, fluoranthene, fluorene, and naphthalene aromatic cores were synthesized to investigate their interactions with DNA, RNA, and G-quadruplex structures. Among the novel compounds, the phenanthrene-guanidino compound demonstrated the highest micromolar affinity for AT-DNA, possibly due to partial phenanthrene intercalation in addition to hydrogen bonding and electrostatic interactions of guanidine cation. All new guanidino-aryl GA compounds bind strongly to the Tel22 G-quadruplex structure with similar affinities regardless of aromatic core size. The 1:1 stoichiometric complex is stabilised by π-π stacking interactions with the top or bottom G-tetrad, together with strong electrostatic interactions of the guanidino cation. The guanidino-porphyrin PoGU displayed distinct binding stoichiometry, indicating possible sandwiching between two G-quadruplex structures. Within the GA compounds tested, guanidino-fluorene exhibited moderate antimetabolic activity against the HeLa cell line, without selectivity against the healthy cell line.
Source: Molecules
Institution: Ruđer Bošković Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
Funder: Hrvatska Zaklada za Znanost
Awards: Spatial Modulations of Guanidines, HRZZ DOK-NPOO — Ruđer Bošković Institute in Zagreb, G2642606078, New peptide-oligonucleotide-chromophore conjugates for biochemical diagnostics and bioactivity, The orchestration of acquired ovarian cancer invasiveness in a stem cell-supporting environment, G6121157870, Molecular recognition of DNA:RNA hybrid and multistranded structures in bioanalytical and in vitro systems
OpenAlex ID: W4414094579