Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Saudi J Biol Sci
2020 Dec 01;2712:3274-3289. doi: 10.1016/j.sjbs.2020.09.041.
Show Gene links
Show Anatomy links
Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs.
Padmini R
,
Uma Maheshwari V
,
Saravanan P
,
Woo Lee K
,
Razia M
,
Alwahibi MS
,
Ravindran B
,
Soliman Elshikh M
,
Ock Kim Y
,
Kim H
,
Kim HJ
.
???displayArticle.abstract???
Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC-MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5-2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.
Fig. 1. Methodology of the in silico Molecular Docking analysis.
Fig. 2. GC–MS chromatogram of ethanol extract of A.sativum.
Fig. 3. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with wild type EGFR (PDB Id: 1 M17) refined by MD simulations.
Fig. 4. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with double mutant EGFR (PDB Id: 5XGN) refined by MD simulations.
Fig. 5. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with exon mutant EGFR (PDB Id: 4LRM) refined by MD simulations.
Fig. 6. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with exon mutant EGFR (PDB Id: 3PP0) refined by MD simulations.
Fig. 7. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with sPLA2-IIA (PDB Id: 5G3N) refined by molecular dynamics simulations.
Fig. 8. The inter-molecular interactions of the phytocompounds, a) Methanone b) Oxazole and c) Bis-Phenylethyl with EML4-ALK (PDB Id: 4Z55) refined by molecular dynamics simulations.
Abdullah Al-Dhabi,
In Vitro Antibacterial, Antifungal, Antibiofilm, Antioxidant, and Anticancer Properties of Isosteviol Isolated from Endangered Medicinal Plant Pittosporum tetraspermum.
2015, Pubmed
Abdullah Al-Dhabi,
In Vitro Antibacterial, Antifungal, Antibiofilm, Antioxidant, and Anticancer Properties of Isosteviol Isolated from Endangered Medicinal Plant Pittosporum tetraspermum.
2015,
Pubmed
Aertgeerts,
Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein.
2011,
Pubmed
Al-Dhabi,
Quantification of Phytochemicals from Commercial Spirulina Products and Their Antioxidant Activities.
2016,
Pubmed
Alonso,
Combining docking and molecular dynamic simulations in drug design.
2006,
Pubmed
Banaganapalli,
Experimental and computational studies on newly synthesized resveratrol derivative: a new method for cancer chemoprevention and therapeutics?
2013,
Pubmed
Bankovic,
Identification of genes associated with non-small-cell lung cancer promotion and progression.
2010,
Pubmed
Barathikannan,
Chemical analysis of Punica granatum fruit peel and its in vitro and in vivo biological properties.
2016,
Pubmed
Bjelkmar,
Implementation of the CHARMM Force Field in GROMACS: Analysis of Protein Stability Effects from Correction Maps, Virtual Interaction Sites, and Water Models.
2010,
Pubmed
Chen,
Synthesis and molecular docking studies of xanthone attached amino acids as potential antimicrobial and anti-inflammatory agents.
2017,
Pubmed
Cheng,
Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants.
2016,
Pubmed
Cuong,
Medically important carotenoids from Momordica charantia and their gene expressions in different organs.
2017,
Pubmed
Daga,
Current drugs and drug targets in non-small cell lung cancer: limitations and opportunities.
2015,
Pubmed
Elango,
Cocos nucifera coir-mediated green synthesis of Pd NPs and its investigation against larvae and agricultural pest.
2017,
Pubmed
Elango,
Spectroscopic investigation of biosynthesized nickel nanoparticles and its larvicidal, pesticidal activities.
2016,
Pubmed
Fleischauer,
Garlic and cancer: a critical review of the epidemiologic literature.
2001,
Pubmed
Fowsiya,
Photocatalytic degradation of Congo red using Carissa edulis extract capped zinc oxide nanoparticles.
2016,
Pubmed
Galli,
Uncommon mutations in epidermal growth factor receptor and response to first and second generation tyrosine kinase inhibitors: A case series and literature review.
2018,
Pubmed
Garrido-Castro,
HER2 driven non-small cell lung cancer (NSCLC): potential therapeutic approaches.
2013,
Pubmed
Giordanetto,
Discovery of AZD2716: A Novel Secreted Phospholipase A2 (sPLA2) Inhibitor for the Treatment of Coronary Artery Disease.
2016,
Pubmed
Glorybai,
Some biological activities of Epaltes divaricata L. - an in vitro study.
2015,
Pubmed
Gummadi,
Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: wild type and mutant (L1196M) active compounds with unique binding mode.
2013,
Pubmed
Haritha,
Green chemical approach towards the synthesis of SnO2 NPs in argument with photocatalytic degradation of diazo dye and its kinetic studies.
2016,
Pubmed
Hess,
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation.
2008,
Pubmed
Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed
Jang,
Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor.
2018,
Pubmed
Kaowinn,
N-Benzyl-N-methyl-dodecan-1-amine, a novel compound from garlic, exerts anti-cancer effects on human A549 lung cancer cells overexpressing cancer upregulated gene (CUG)2.
2018,
Pubmed
Kim,
PubChem Substance and Compound databases.
2016,
Pubmed
Kong,
Structural pharmacological studies on EGFR T790M/C797S.
2017,
Pubmed
Kurian,
Antioxidant effects of ethyl acetate extract of Desmodium gangeticum root on myocardial ischemia reperfusion injury in rat hearts.
2010,
Pubmed
Lin,
Preliminary screening of some traditional zulu medicinal plants for anti-inflammatory and anti-microbial activities.
1999,
Pubmed
Michellys,
Design and synthesis of novel selective anaplastic lymphoma kinase inhibitors.
2016,
Pubmed
Miladiyah,
Biological activity, quantitative structure-activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs.
2018,
Pubmed
Morris,
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.
2009,
Pubmed
Myneni,
Raw Garlic Consumption and Lung Cancer in a Chinese Population.
2016,
Pubmed
Nand,
Virtual screening of natural compounds as inhibitors of EGFR 696-1022 T790M associated with non-small cell lung cancer.
2016,
Pubmed
Park,
Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus).
2016,
Pubmed
Park,
Composition of volatile compounds and in vitro antimicrobial activity of nine Mentha spp.
2016,
Pubmed
Park,
Accumulation of Carotenoids and Metabolic Profiling in Different Cultivars of Tagetes Flowers.
2017,
Pubmed
Pillai,
HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium.
2017,
Pubmed
Pinkas-Kramarski,
The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin.
1998,
Pubmed
Ricciardi,
NSCLC and HER2: between lights and shadows.
2014,
Pubmed
Rikova,
Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.
2007,
Pubmed
Rom,
Molecular and genetic aspects of lung cancer.
2000,
Pubmed
Saravanan,
Potential selective inhibitors against Rv0183 of Mycobacterium tuberculosis targeting host lipid metabolism.
2012,
Pubmed
Shaik,
Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR.
2019,
Pubmed
Stamos,
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
2002,
Pubmed
Stella,
Targeting EGFR in non-small-cell lung cancer: lessons, experiences, strategies.
2012,
Pubmed
Surendra,
Vegetable Peel Waste for the Production of ZnO Nanoparticles and its Toxicological Efficiency, Antifungal, Hemolytic, and Antibacterial Activities.
2016,
Pubmed
Surendra,
RSM optimized Moringa oleifera peel extract for green synthesis of M. oleifera capped palladium nanoparticles with antibacterial and hemolytic property.
2016,
Pubmed
Surendra,
Phenolic compounds in drumstick peel for the evaluation of antibacterial, hemolytic and photocatalytic activities.
2016,
Pubmed
Valsalam,
Rapid biosynthesis and characterization of silver nanoparticles from the leaf extract of Tropaeolum majus L. and its enhanced in-vitro antibacterial, antifungal, antioxidant and anticancer properties.
2019,
Pubmed
Wieduwilt,
The epidermal growth factor receptor family: biology driving targeted therapeutics.
2008,
Pubmed
Yasuda,
Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer.
2013,
Pubmed
Yu,
Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo.
2012,
Pubmed
Zhang,
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.
2012,
Pubmed
Zhao,
Crystal structure of EGFR T790M/C797S/V948R in complex with EAI045.
2018,
Pubmed
Zheng,
Spices for Prevention and Treatment of Cancers.
2016,
Pubmed
Zoete,
SwissParam: a fast force field generation tool for small organic molecules.
2011,
Pubmed
