New Inhibitors of Respiratory Syncytial Virus (RSV) Replication Based on Monoterpene-Substituted Arylcoumarins

Abstract

Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, there are no vaccines and specific chemotherapeutic agents for the treatment of this disease, so the search for low-molecular weight compounds to combat RSV is a challenge. In this work, we have shown, for the first time, that monoterpene-substituted arylcoumarins are efficient RSV replication inhibitors at low micromolar concentrations. The most active compound has a selectivity index of about 200 and acts most effectively at the early stages of infection. The F protein of RSV is a potential target for these compounds, which is also confirmed by molecular docking and molecular dynamics simulation data.

Therapeutic Potential of Myrtenal and Its Derivatives—A Review

“…According to Bergman, Franks, and Philips (2023), certain acyclic monoterpenes and their derivatives have demonstrated notable anti-inflammatory potential [91]. Several monoterpene-coumarin conjugates showed good antiviral activity [92,93], while others demonstrated the capacity to inhibit the enzyme TDP1, which serves as a pivotal target in the realm of anticancer therapy [94,95]. The same inhibitory activity was demonstrated for some monoterpenes conjugated with various heterocyclic fragments [96,97].…”

Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus

“…As for the control wells, instead of administering the compound, a culture medium containing a similar concentration of DMSO was used. Recently, further research [6] revealed the antiviral activity of structural analogs of K142, which contained 4-aryl-substituted coumarin cores conjugated with monoterpene fragments. Although the most active compounds were found to be less potent than K142, they exhibited slightly better selectivity indexes [6].…”

“…Recently, further research [ 6 ] revealed the antiviral activity of structural analogs of K142, which contained 4-aryl-substituted coumarin cores conjugated with monoterpene fragments. Although the most active compounds were found to be less potent than K142, they exhibited slightly better selectivity indexes [ 6 ]. Therefore, coumarin-monoterpene conjugates hold promise for the development of new anti-RSV agents.…”

“…The leader compound 19c, now having a code name K142 (Figure 1) ((3-(((1S,5R)-6,6-dimethylbicyclo [3.1.1]hept-2-en-2-yl)methoxy)-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one)), demonstrated good activity against both RSV A and B, with a selective index of more than 70 and an IC50 ranging from 4.9-5.1 μM [5]. Recently, further research [6] revealed the antiviral activity of structural analogs of K142, which contained 4-aryl-substituted coumarin cores conjugated with monoterpene fragments. Although the most active compounds were found to be less potent than K142, they exhibited slightly better selectivity indexes [6].…”

New 5-Hydroxycoumarin-Based Tyrosyl-DNA Phosphodiesterase I Inhibitors Sensitize Tumor Cell Line to Topotecan

“…Coumarin-monoterpene conjugates 33-38 were obtained by reaction of 5-hydroxycoumarins 26-31 with corresponding monoterpenoid bromides 32a-d in the presence of DBU and DMF, as described previously [39,40] (Scheme 3). The products were obtained in yields 44-89% following purification by either recrystallization or column chromatography.…”