Guanidino-Aryl Derivatives: Binding to DNA, RNA and G-Quadruplex Structure and Antimetabolic Activity

Margetić, Davor; Jadrijević-Mladar, Petra; Brozović, Anamaria; Tumir, Lidija-Marija (2025) Guanidino-Aryl Derivatives: Binding to DNA, RNA and G-Quadruplex Structure and Antimetabolic Activity. Molecules, 30 (18). ISSN 1420-3049

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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.

Item Type:	Article
Uncontrolled Keywords:	aryl-guanidine; fluorescence; circular dichroism; DNA binding; RNA binding; G-quadruplex
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Molecular Biology Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Molekularno prepoznavanje DNA:RNA hibridnih i višelančanih struktura u bioanalitičkim i in vitro sustavima-DNARNAHyB-MolBio Marijana Radić Stojković IP-2018-01-4694 HRZZ Novi peptid-oligonukleotid-kromofor konjugati za biokemijsku dijagnostiku I bioaktivnost Ivo Piantanida IP-2022-10-9829 HRZZ Prostorne modulacije gvanidina Davor Margetić IP-2022-10-4385 HRZZ Regulacija stečene invazivnosti raka jajnika u okruženju koje podržava rast matičnih stanica Anamaria Brozovic IP-2022-10-5202 HRZZ
Depositing User:	Lorena Palameta
Date Deposited:	04 Nov 2025 09:33
URI:	http://fulir.irb.hr/id/eprint/10131
DOI:	10.3390/molecules30183682

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