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A series of amphiphilic conjugates of dihydroxy selenolane (DHS) and monoamine selenolane (MAS), which we had previously reported to inhibit lipid peroxidation and assist the oxidative protein folding reaction respectively in cell free systems, were evaluated for cytotoxicity, associated mechanisms and antioxidant effects in cells. Our results indicated that a fatty acid/alkyl group of variable chain lengths (C 6-14 ) as a lipophilic moiety of the DHS/MAS conjugates not only improved their ability to incorporate within the plasma membrane of cells but also modulated their cytotoxicity. In the concentration range of 1-50 μM, C 6 conjugates were non-toxic whereas the long chain (≥C 8 ) conjugates showed significant cytotoxicity. The induction of toxicity investigated by the changes in membrane leakage, fluidity, mitochondrial membrane potential and annexin-V-propidium iodide (PI) staining by using flow cytometry revealed plasma membrane disintegration and subsequent induction of necrosis as the major mechanism. Further, the conjugates of DHS and MAS also showed differential as well as nonlinear tendency in cytotoxicity with respect to chain lengths and this effect was attributed to their self-aggregation properties. Compared with the parent compounds, C 6 conjugates not only exhibited better antioxidant activity in terms of the induction of selenoproteins such as glutathione peroxidase 1 (GPx1), GPx4 and thioredoxin reductase 1 (TrxR1) but also protected cells from the AAPH induced oxidative stress. In conclusion, the present study suggests the importance of hydrophilic-lipophilic balance (HLB) in fine tuning the toxicity and activity of bioinspired amphiphilic antioxidants.

Understanding of the efficacy and mechanism for the reaction of the biologically important radicals with natural and/or synthetic antioxidants is the first step towards the development of future therapeutic agents. The kinetic parameters e.g., formation and decay rate constants predict the efficacy of an antioxidant and its fate after reaction. These parameters also dictate the ease with which competing reactions would occur in a bio-environment. The spectroscopic parameters provide the clue to the site of free radical attack to these antioxidants. Here, in this article an attempt has been made to show the use of physico-chemical methods in the evaluation of antioxidant activity of some important medicinal plants commonly used in India and the subcontinent. The systems chosen here for discussions are herbal extracts as such, curcumin from turmeric, methoxy phenols from Indian spices, dehydrogingerdione from ginger and bakuchiol from Psoralea corylifolia. All the examples shown in this article illustrate the potential of the pulse radiolysis coupled with kinetic spectroscopy and other physicochemical techniques for the study of antioxidants either in the form of mixture as in herbal extract or as an isolated compound.