Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy

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...

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Autores principales:	Bhargav Shreevatsa, Chandan Dharmashekara, Vikas Halasumane Swamy, Meghana V. Gowda, Raghu Ram Achar, Vivek Hamse Kameshwar, Rajesh Kumar Thimmulappa, Asad Syed, Abdallah M. Elgorban, Salim S. Al-Rejaie, Joaquín Ortega-Castro, Juan Frau, Norma Flores-Holguín, Chandan Shivamallu, Shiva Prasad Kollur, Daniel Glossman-Mitnik
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NQO1 virtual screening molecular docking Nrf2 detoxification phytobiactives Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/f039d1eae82d4a3b8bc5c8c39db5e75f
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spelling	oai:doaj.org-article:f039d1eae82d4a3b8bc5c8c39db5e75f2021-11-25T18:27:55ZVirtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy10.3390/molecules262268631420-3049https://doaj.org/article/f039d1eae82d4a3b8bc5c8c39db5e75f2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6863https://doaj.org/toc/1420-3049NAD(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.Bhargav ShreevatsaChandan DharmashekaraVikas Halasumane SwamyMeghana V. GowdaRaghu Ram AcharVivek Hamse KameshwarRajesh Kumar ThimmulappaAsad SyedAbdallah M. ElgorbanSalim S. Al-RejaieJoaquín Ortega-CastroJuan FrauNorma Flores-HolguínChandan ShivamalluShiva Prasad KollurDaniel Glossman-MitnikMDPI AGarticleNQO1virtual screeningmolecular dockingNrf2detoxificationphytobiactivesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6863, p 6863 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NQO1 virtual screening molecular docking Nrf2 detoxification phytobiactives Organic chemistry QD241-441
spellingShingle	NQO1 virtual screening molecular docking Nrf2 detoxification phytobiactives Organic chemistry QD241-441 Bhargav Shreevatsa Chandan Dharmashekara Vikas Halasumane Swamy Meghana V. Gowda Raghu Ram Achar Vivek Hamse Kameshwar Rajesh Kumar Thimmulappa Asad Syed Abdallah M. Elgorban Salim S. Al-Rejaie Joaquín Ortega-Castro Juan Frau Norma Flores-Holguín Chandan Shivamallu Shiva Prasad Kollur Daniel Glossman-Mitnik Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
description	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.
format	article
author	Bhargav Shreevatsa Chandan Dharmashekara Vikas Halasumane Swamy Meghana V. Gowda Raghu Ram Achar Vivek Hamse Kameshwar Rajesh Kumar Thimmulappa Asad Syed Abdallah M. Elgorban Salim S. Al-Rejaie Joaquín Ortega-Castro Juan Frau Norma Flores-Holguín Chandan Shivamallu Shiva Prasad Kollur Daniel Glossman-Mitnik
author_facet	Bhargav Shreevatsa Chandan Dharmashekara Vikas Halasumane Swamy Meghana V. Gowda Raghu Ram Achar Vivek Hamse Kameshwar Rajesh Kumar Thimmulappa Asad Syed Abdallah M. Elgorban Salim S. Al-Rejaie Joaquín Ortega-Castro Juan Frau Norma Flores-Holguín Chandan Shivamallu Shiva Prasad Kollur Daniel Glossman-Mitnik
author_sort	Bhargav Shreevatsa
title	Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
title_short	Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
title_full	Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
title_fullStr	Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
title_full_unstemmed	Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy
title_sort	virtual screening for potential phytobioactives as therapeutic leads to inhibit nqo1 for selective anticancer therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f039d1eae82d4a3b8bc5c8c39db5e75f
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Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy

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