Combined experimental and in silico approaches for exploring antiperoxidative potential of structurally diverse classes of antioxidants on docetaxel-induced lipid peroxidation using 4-HNE as the model marker

• Role of antioxidants on docetaxel-induced lipid peroxidation was explained.
• Both experimental and in silico approaches were taken to the work.
• The experimental study was performed in vitro.
• The computational study was performed with freely available 2D descriptors.
• The developed QSAR model was validated rigorously using several validation techniques.

The objective of the present work was tantamount to explain the antiperoxidative potential and structural requirements of twenty-eight structurally diverse classes of antioxidants on docetaxel-induced lipid peroxidation. Both experimental and computational approaches were taken to the work. The experiments were performed in vitro and goat liver was used as a source of lipid. 4-hydroxy-2-nonenal was used as model marker for estimation of docetaxel–lipid interaction. The computational portion of the work was limited to QSAR analysis of those antioxidants for better understanding of the structural requirements of antioxidants on docetaxel–lipid interaction. The study was done with freely online available 2D descriptors available on PaDEL (open source). Stepwise regression analysis was used as chemometric tool. The experimental study showed the lipid peroxidation induction capacity of docetaxel. It was also noted that all twenty-eight antioxidants had the ability to suppress the lipid peroxidation. But among them butylated hydroxyl toluene showed the highest potential (−20.5%) and flavone showing lowest potential (−0.8%) to suppress the docetaxel-induced lipid peroxidation. The computational study indicates the importance of topology of the whole molecules, topological distances among atoms within a molecule and specific fragment pattern present in a molecule required for inhibition of lipid peroxidation.

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