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Synthesis, Characterization and Biological Activity of Hydroxamic Acids Derived from Olive Oil Triacylglycerides

Purpose: In this study, we report about the use of olive oil as starting material for preparation of fatty hydroxamic acids (FHAs) and the results of biological activity testing. Material and Methods: FHAs were synthesized by hydroxylaminolysis of triglycerides from olive oil (Scheme 1). The structures of the compounds were deduced from their elemental analysis, IR and NMR data. One- and two-dimensional homo- and heteronuclear 1H and 13C NMR measurements have revealed some interesting features of these compounds. FHAs mixture were investigated for their antioxidant activity using three assays: radical scavenging activity for DPPH free radical, ability to chelate ferrous ions and antioxidant activity in β-carotene bleaching assay. FHAs biological effects on cell toxicity were assessed by MTT test in normal fibroblast cell line (BJ) and tumour cell line (HeLa). Scheme 1.Results: Elemental analysis, IR, 1H and 13C NMR spectroscopy data showed that obtained FHAs are N-oleoyl hydroxamic acid (OHA) with small amount of N-linoleyl hydroxamic acid (LHA). The results of in vitro assays showed that FHAs possess notable antioxidant, radical-scavenging and chelating properties. FHAs affected more normal cells (fibroblasts) by reducing their growth while the effect on fast growing tumor cell line was mild, probably reflecting differences in metabolism of these cell lines. Molinspiration drug-likeness scores of OHA were computed for enzyme (0.55) and protease inhibitor (0.58), while of oleic acid (OA) for nuclear receptor ligand (0.23) and enzyme inhibitor (0.27). ADMET Predictor properties indicated OHA as CYP 2E1 substrate, and OA as non-substrate. The ADMET risk and TOX MUT risk of OHA are 2.0 and TOX risk 0.0, while the same parameters for OA are 4.0, 0.0 and 1.0, respectively. Conclusions: The described method of FHAs preparation from olive oil is convenient method for the determination of triacylglycerides composition in different oils. The results of preliminary in vitro assays and antitumor activity on HeLa cell line showed that FHAs are compounds with antioxidant and antiradical properties, as well as with antitumor activity. Reference: Hoidy WH, Ahmad MB, Al-Mulla EA, Yunus WM, Bt Ibrahim N, J. Oleo Sci. 59(1), 2010, 15-19.

Fatty hydroxamic acids; olive oil triacylglycerides; 1H and 13C NMR spectroscopy; biological activity; antioxidant activity; cell toxicity; ADMET properties

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