DNA sequence-specific ligands. XX. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric trisbenzimidazoles DB3P(n)

• Published in: Medicinal chemistry research 2023-03, Vol.32 (3), p.587-599
• Main Authors: Arutyunyan, Albert F., Kostyukov, Alexey A., Lushpa, Vladislav A., Mineev, Konstantin S., Korolev, Sergey P., Gottikh, Marina B., Klimova, Regina R., Kushch, Alla A., Kalabina, Kseniya V., Susova, Olga Yu, Zhuze, Alexei L.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biological properties; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; DNA biosynthesis; DNA topoisomerase; DNA viruses; Fluorescence; Grooves; HIV; Human immunodeficiency virus; Inorganic Chemistry; Integrase; Ligands; Medicinal Chemistry; Nuclear membranes; Nucleotide sequence; Original Research; Pharmacology/Toxicology; Synthesis
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03017-x

A new series of AT-specific minor groove DNA ligands (DB 3 P( n ); n  = 1,2,3,4) was synthesized and their spectral, biological and virological properties were investigated. With a methylene spacers of different lengths blocks of three AT pairs located at different distances from each other could be recognized. The compounds synthesized suppressed the activity of HIV-1 integrase at submicromolar concentrations (0.25–0.50 µМ). Also, DB 3 P( n ) were found to be effective inhibitors of simplex virus type I and DNA topoisomerase I. The synthesized DB 3 P( n ) demonstrated good solubility in water, could penetrate through cell and nuclear membranes, and stain DNA in live cells. Graphical Abstract