Reactive oxygen species (ROS) are widely known as highly reactive signalling and transcription factors. They have shown beneficial effects at low concentrations to regulate multiple cellular processes like proliferation, differentiation, migration, necrosis, and autophagy. Elevated levels of ROS destroys the physiological functions by cross-linking with lipids, protein, and DNA, which lead to several diseases, including cancer, cardiovascular, diabetes, arthritis, neurological disorders and others metabolic diseases. Thus, quenching of excess ROS is very necessary to counter their deleterious effects. To deplete their increased concentration, there are so many endogenous as well as exogenous antioxidants are available, including both enzymatic and non-enzymatic antioxidants. In this review, we have discussed the numerous sources that generate several type of free radical/non- radical species such as superoxide and nitric oxide, singlet oxygen, nitroxyl anion, nitrosyl cation, hypochlorous acid, etc. In terms of molecular mechanism, we also discussed the role of endogenous (enzymatic, and non-enzymatic) and exogenous antioxidants (vitamins, plant-derived and other small molecules), including ascorbic acids, β-carotene, α-tocopherol, α-lipoic acid, coenzyme Q10, melatonin, and flavonoids (quercetin, luteolin, kaempferol, epicatechin, catechin, daidzein, genistein, and rutin, etc.) in scavenging of ROS. This review described sources and generation of ROS, associated diseases, and antioxidants, mainly focusing on molecular mechanisms. In addition, signaling pathways such as NF-κB, MAPKs, and Keap1-Nrf2-ARE etc., which affects physiological functions of ROS, are also discussed in details. Graphical abstract

A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking analysis revealed that among all derivatives of SOXs (4a–4h), 4a has a substantial binding affinity (∆G) −6.65, −6.55, −8.73, and −7.27 Kcal/mol with CD-44, EGFR, AKR1D1, and HER-2, respectively. A functional study demonstrated that SOX 4a has a substantial impact on human cancer cell phenotypes exhibiting abnormality in cytoplasmic and nuclear architecture as well as granule formation leading to cell death. SOX 4a treatment robustly induced reactive oxygen species (ROS) generation in cancer cells as observed by enhanced DCFH-DA signals. Overall, our results suggest that SOX (4a) targets CD-44, EGFR, AKR1D1, and HER-2 and induces ROS generation in cancer cells. We conclude that SOX (4a) could be explored as a potential chemotherapeutic molecule against various cancers in appropriate pre-clinical in vitro and in vivo model systems.