Antioxidant and cytotoxic activity of mono- And bissalicylic acid derivatives

Abstract

A simple synthesis of mono- and bis-salicylic acid derivatives 1-10 by the transesterification of methyl salicylate (methyl 2-hydroxybenzoate) with 3-oxapentane-1,5-diol, 3,6-dioxaoctane-1,8-diol, 3,6,9-trioxaundecane-1,11-diol, propane-1,2-diol or 1-aminopro-pan-2-ol in alkaline conditions is reported. All compounds were tested in vitro on three malignant cell lines (MCF-7, MDA-MB-231, PC-3) and one non-tumor cell line (MRC-5). Strong cytotoxicity against prostate PC-3 cancer cells expressed compounds 3, 4, 6, 9 and 10, all with the IC50 less than 10 μmol/L, which were 11-27 times higher than the cytotoxicity of antitumor drug doxorubicin. All tested compounds were not toxic against the non-tumor MRC-5 cell line. Antioxidant activity of the synthesized derivatives was also evaluated. Compounds 2, 5 and 8 were better OH radical scavengers than commercial antioxidants BHT and BHA. The synthesized compounds showed satisfactory scavenger activity, which was studied by QSAR modeling. A good correlation between the experimental IC50DPPH and IC50OH and MTI (molecular topological indices) molecular descriptors and CAA (accessible Connolly solvent surface area) for the new compounds 1, 3, and 5 was observed.