Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells

Frontiers in Pharmacology
Onat KadiogluVincent K W Wong

Abstract

Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggab...Continue Reading

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Citations

Jun 7, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Yang-Shuo TangQiao-Ling Zhou
Nov 19, 2019·Current Topics in Medicinal Chemistry·Prasath ManogaranViswanadha Vijaya Padma
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Dec 17, 2020·Journal of Biochemical and Molecular Toxicology·Fatemeh YarmohammadiGholamreza Karimi
Jan 9, 2021·Redox Report : Communications in Free Radical Research·Nabila JahanSicen Wang
May 28, 2019·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Christian Bailly

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Stardrop
VMD
ADME QSAR
AutoDock
Derek Nexus

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