In Vitro Study of Antiviral Properties of Compounds Based on 1,4-Dioxane Derivative of Closo-Decaborate Anion with Amino Acid Ester Residues Against Influenza Virus A/IIV-Orenburg/83/2012(H1N1)pdm09

体外研究基于1,4-二氧杂环己烷衍生物的含氨基酸酯残基的闭合十硼酸根阴离子化合物对甲型流感病毒A/IIV-Orenburg/83/2012(H1N1)pdm09的抗病毒性能

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Abstract

New derivatives of the closo-decaborate anion [B(10)H(9)-O(CH(2))(2)O(CH(2))(3)C(O)-L-OCH(3)](2-) (An) (1: L = Trp; 2: L = His; 3: L = Met; 4: L = Ala(2-oxopyrrolidin-3-yl) (Pld) were synthesized and isolated as tetraphenylphosphonium salts (Ph(4)P)(2)An. Anions 1(2-); 2(2-); 3(2-), and 4(2-) contain a pendant functional group from the L-tryptophan methyl ester, L-histidine methyl ester, L-methionine methyl ester, or methyl 2-amino-3-(2-oxopyrrolidin-3-yl)propanoate (-Trp-OCH(3), -His-OCH(3), -Met-OCH(3), or -Pld-OCH(3)) residue, respectively, bonded with the boron cluster anion through the oxybis[(ethane-2,1-diyl)oxy] spacer. This pacer is formed as a result of the nucleophilic opening of the attached dioxane molecule in the [B(10)H(9)O(CH(2))(4)O](-) starting derivative. Sodium salts of the target compounds were isolated and used in biological experiments. It was established that among compounds Na(2)An (An = 1-4), not all are capable of inhibiting the cytopathic effect of the virus in vitro. Sodium salts Na(2)An have a low toxic effect on a monolayer of continuous canine embryonic kidney (MDCK) cell line. Compounds Na(2)1 and Na(2)2 had IC(50) of 5.0 and 20.0 μg/mL, respectively, while for compounds Na(2)3 and Na(2)4, IC(50) values could not be achieved at the concentrations studied. The studies performed for molecular docking of the anionic part of 1(2-) and 2(2-) with the transmembrane domain of viroporin M2 show some differences in the location of these two ligands inside the M2 canal pore.

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