Abstract
NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.
Highlights
NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is one of the two main quinone reductases in the mammalian system
These results implicate that Orientin binding with NQO1 is very strong as compared to other compounds (see Table S2 of the Figure 11 shows that the two-Dimensional and three-Dimensional visualisation of the phytobioactives docked against the NQO1 (2F1O) protein exhibits an interaction, i.e., hydrogen bonding and other lower interactions like Van der Waals force, π − π stacked, π − π T-shaped, π-alkyl and carbon-hydrogen bond
The phytoactive compounds such as Orientin, Trimethadione, Alliin, and some other potent plant-derived molecules from a range of chemical classes has shown better interaction towards the NQO1 protein when compared to the standard
Summary
NQO1 is one of the two main quinone reductases in the mammalian system. The paralog of cytosolic protein NQO1 is NQO2. NQO1 is involved in shielding cells from a range of harmful compounds, including quinones and other reactive oxygen species (ROS) Apart from this, it plays a significant role in p53 stabilization [9]. Nrf2-induced over expression of NQO1 can play a significant role in chemotherapy failures, where it may be an adaptive response to oxidative stress and cytotoxicity and provide cancer cells with defense [14]. A study has revealed that β-lapachone from the bark of the lapacho tree affects the expression of NQO1 by mediating the inactivation of the Akt/mTOR pathway, resulting in significant anti-proliferation and anti-metastasis effects in breast cancer cell lines [25]. The potency of the phytobioactives was evaluated by MD simulation studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
