<i>In vitro</i> study of antiviral properties of compounds based on tetrahydropyran derivative of <i>closo</i>-decaborate anion with amino acid ester residues against influenza virus A/IIV-Orenb

Based on the substituted derivative of the decahydro-closo-decaborate anion (Ph4P)2[B10H9O(CH2)5COOH] obtained by opening the tetrahydropyran substituent in the anion [B10H9O(CH2)5]–, a series of compounds Na2[B10H9O(CH2)6C(O)X], where X = Trp-OMe (1), His-OMe (2), Met-OMe (3), Pld-OMe (4), containing various amino acid substituents attached to the pendant carboxyl group, were synthesized. The compounds were isolated as sodium salts. The residues of L-tryptophan (Na21) and L-histidine (Na22) contained aromatic heterocyclic groups indole and imidazole, respectively, as a side group. Compounds Na23 and Na24 contained substituted alkanes as a side group: L-methionine (Na23) contained a methyl ethyl sulfide group, and compound Na24 contained the residue of an aliphatic synthetic amino acid in which the side group was represented by γ-butyrolactam (pyrrolidin-2-one). Compounds Na21 and Na22 were found to exhibit dose-dependent antiviral activity against the influenza virus strain A/IIV-Orenburg/83/2012(H1N1)pdm09 in vitro. IC50 for compound Na21 was 5.0 μg/ml, and for compound Na22 it was found to be 10.0 μg/ml. Molecular docking of the M2 protein pore and compounds Na21 and Na22 was performed. It was found that the most probable arrangement of molecules in the pore of the M2 channel is associated with the location of the heterocycle inside the pore of the M2 channel in the region of the residues His37–Trp41, and for the compound Na21 this an arrangement is more favorable than for Na22, which explains some difference in the concentrations of suppression of viral reproduction for Na21 and Na22. For compounds Na23and Na24, antiviral activity was not detected.