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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Antimetastatic Potential of Quercetin Analogues with Improved Pharmacokinetic Profile: A Pharmacoinformatic Preliminary Study

Author(s): Nebojša Pavlović*, Nastasija Milošević, Maja Đjanić, Svetlana Goločorbin-Kon, Bojan Stanimirov, Karmen Stankov and Momir Mikov

Volume 22, Issue 7, 2022

Published on: 08 June, 2021

Page: [1407 - 1413] Pages: 7

DOI: 10.2174/1871520621666210608102452

Price: $65

Abstract

Background: Urokinase-type plasminogen activator (uPA) system is a crucial pathway for tumor invasion and metastasis. Recently, multiple anticancer effects of quercetin have been described, including inhibitory activity against uPA. However, the clinical use of this flavonoid has been limited due to its low oral bioavailability.

Objective: The objectives of the study were to assess the antimetastatic potential of quercetin analogues by analyzing their binding affinity for uPA, and to select the compounds with improved pharmacological profiles.

Methods: Binding affinities of structural analogues of quercetin to uPA receptor were determined by molecular docking analysis using Molegro Virtual Docker software, and molecular descriptors relevant for estimating pharmacological profile were calculated from ligand structures using computational models.

Results: Among 44 quercetin analogues, only one quercetin analogue (3,6,2’,4’,5’-pentahydroxyflavone) was found to possess higher aqueous solubility and membrane permeability, and stronger affinity for uPA than quercetin, which makes it a potential lead compound for anticancer drug development. Like quercetin, this compound has five hydroxyl groups, but arranged differently, which contributes to the higher aqueous solubility and higher amphiphilic moment in comparison to quercetin. Since membrane permeability is not recognized as the limiting factor for quercetin absorption, analogues with higher aqueous solubility and retained or stronger uPA inhibitory activity should also be further experimentally validated for potential therapeutic use.

Conclusion: Identified quercetin analogues with better physicochemical and pharmacological properties have a high potential to succeed in later stages of research in biological systems as potential anticancer agents with antimetastatic activity.

Keywords: Molecular docking, quercetin, analogues, cancer, uPA, pharmacokinetics.

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