DNA sequence-specific ligands. XVII. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric bisbenzimidazoles DBA(n)

• Published in: Bioorganic & medicinal chemistry Vol. 26; no. 9; pp. 2302 - 2309
• Main Authors: Koval, Vasiliy S., Arutyunyan, Albert F., Salyanov, Victor L., Klimova, Regina R., Kushch, Alla A., Rybalkina, Ekaterina Yu, Susova, Olga Yu, Zhuze, Alexei L.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.05.2018; Elsevier
• Subjects: Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - toxicity; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - toxicity; Biochemistry & Molecular Biology; Cattle; Cell Line, Tumor; Cell Nucleus - metabolism; Cercopithecus aethiops; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytomegalovirus - drug effects; DNA - chemistry; Fluorescence; Herpesvirus 1, Human - drug effects; Humans; Life Sciences & Biomedicine; Ligands; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Solubility; Topoisomerase I Inhibitors - chemical synthesis; Topoisomerase I Inhibitors - chemistry; Topoisomerase I Inhibitors - toxicity; Vero Cells; PBS; BOP; scDNA; b.p; MABs; DIPEA; TBTU; DMT; CMV; NMM; HSV-1; topo-I; ACV; IC50; Phth-GlyOH; PFU/cells; HOECHST-33258; BINDING; INHIBITION
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2018.03.018

[Display omitted] A series of DNA minor groove binding fluorescent dimeric bisbenzimidazoles DBA(n) bearing linkers of various length were synthesized and their biochemical and antiviral activities were evaluated. Their antiviral activity was assessed in model cell systems infected with human herpes simplex virus (HSV-1) and cytomegalovirus (CMV). Compounds DBA(1) and DBA(7) demonstrated in vitro inhibitory properties towards HSV-1, and DBA(7) completely blocked the viral infection. Compound DBA(11) displayed the in vitro therapeutic activity towards both HSV-1 and CMV. All of the DBA(n) could fluoresce, were well soluble in water, not cytotoxic to a concentration of 240 µM, penetrated well into cell nuclei by binding to DNA and could inhibit topo-I at low micromolecular concentrations.