Medicinal Chemistry

Cytotoxic and Antiviral Properties of Novel Dehydroabietylamine Salts

Abstract

Kseniya S Kovaleva, Alena A Kononova, Vlad A Korobeynikov, Sergey V Cheresiz, Vladimir V Zarubaev, Anna A Shtro, Yana R Orshanskaya, Olga I Yarovaya, Andrey G Pokrovsky and Nariman F Salakhutdinov

Here, we report the synthesis of a series of dehydroabietylamine (DAA) salts. We studied the cytotoxic activity of DAA salts and their and antiviral properties against influenza virus A(H1N1)pdm09 We further compared these parameters to those of DAA itself and to organic acids used as counterions. We observed that the DAA, its hydrochloride (DAAâË?â?¢HCl) and organic salts had similar cytotoxicity profiles in three cancer cell lines: MDA-MB-231, MCF-7, U-87 MG. Meanwhile the cytotoxicity of same organic salts of DAA with respect to melanoma cell line SK-Mel-8 was higher than those DAA and DAAâË?â?¢HCl: CTD50 values of 5 from 14 synthesized salts were 2-2.8 times lower than that of CTD50 for DAAâË?â?¢HCl. Pure organic acids used for the synthesis of DAA salts were noncytotoxic to cancer cells, except ursolic and glycyrrhetic acid having moderate cytotoxicity. Further, we found that modification of DAA with counterions derived from the selected organic acids does not affect, in most cases, the DAA antiviral activity (except compound 4n, DAA glycyrrhetate). The toxicity of this compound was significantly lower than that of its constituting ions, thereby making the selectivity index of this compound against the A(H1N1) pdm09 virus several times higher than that of other DAA salts.