MyMedR

Displaying all 12 publications

Abstract:

Sort:

Differential proteomic analysis on the effects of 2-methoxy-1,4-naphthoquinone towards MDA-MB-231 cell line

Liew K, Yong PV, Navaratnam V, Lim YM, Ho AS

Phytomedicine, 2015 May 15;22(5):517-27.
PMID: 25981917 DOI: 10.1016/j.phymed.2015.03.007

We have previously reported the anti-metastatic effects of 2-methoxy-1,4-naphthoquinone (MNQ) against MDA-MB-231 cell line.

Matched MeSH terms: Naphthoquinones/pharmacology*
Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene hybrids and their antimycobacterial evaluation

Devi Bala B, Muthusaravanan S, Choon TS, Ashraf Ali M, Perumal S

Eur J Med Chem, 2014 Oct 6;85:737-46.
PMID: 25129868 DOI: 10.1016/j.ejmech.2014.08.009

A general method for the synthesis of a library of hitherto unreported amino-1,4-naphthoquinone-appended triazoles was accomplished via a sequential three-component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene-triazole hybrid heterocycles were also synthesized from the amino-1,4-naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 μM, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50

Matched MeSH terms: Naphthoquinones/pharmacology*
Fulltext 2-Methoxy-1,4-Naphthoquinone (MNQ) Inhibits Glucose Uptake and Lactate Production in Triple-Negative Breast Cancer Cells

Daud SM, Yaacob NS, Fauzi AN

Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):59-65.
PMID: 33576213 DOI: 10.31557/APJCP.2021.22.S1.59

OBJECTIVE: The persistent activation of aerobic glycolysis in cancer cells results in accumulation of lactate and other metabolic intermediates that contribute to tumorigenesis. Increased glycolysis is frequently dysregulated in triple-negative breast cancer (TNBC), which promotes tumor growth and immune escape. This study was conducted to investigate the effect of 2-methoxy-1, 4-naphthoquinone (MNQ), compound extracted from Impatiens balsamina on glycolytic activities in human breast adenocarcinoma, MDA-MB-231 cells.
METHODS: Initially, MTT proliferation assay was used to test the cell viability with various doses of MNQ (5-100 µM). As the half maximal inhibitory concentration (IC50) was obtained, glucose uptake and lactate assays of the cells were tested with IC50 dose of MNQ. The treated cells were also subjected to gene and protein analysis of glycolysis-related molecules (GLUT1 and Akt).
RESULTS: The results showed that MNQ decreased the percentage of MDA-MB-231 cell viability in a dose-dependent manner with the IC50 value of 29 µM. The percentage of glucose uptake into the cells and lactate production decreased significantly after treatment with MNQ as compared to untreated cells. Remarkably, the expressions of GLUT1 and Akt molecules decreased in MNQ-treated cells, suggesting that the inhibition of glycolysis by MNQ is GLUT1-dependent and possibly mediated by the Akt signaling pathway.
CONCLUSION: Our findings indicate the ability of MNQ to inhibit the glycolytic activities as well as glycolysis-related molecules in MDA-MB-231 cells, suggesting the potential of MNQ to be further developed as an effective anticancer agent against TNBC cells.

Matched MeSH terms: Naphthoquinones/pharmacology*
Monoamine oxidase inhibitory naphthoquinone and/or naphthalene dimers from Lemuni Hitam (Diospyros sp.), a Malaysian herbal medicine

Okuyama E, Homma M, Satoh Y, Fujimoto H, Ishibashi M, Yamazaki M, et al.

Chem Pharm Bull (Tokyo), 1999 Oct;47(10):1473-6.
PMID: 10553643

From the extract of a Malaysian herbal medicine, Lemuni Hitam (Diospyros sp.), which exhibited monoamine oxidase (MAO) inhibition, three new naphthoquinone and/or naphthalene dimers (lemuninols A-C, 1-3) were isolated together with 4,6-dihydroxy-5-methoxy-2-methyl-naphthalene (8) and six known monomers (4-7, 9 and 10). The structures were determined by spectroscopic methods including 2D-NMR techniques. Among them, lemuninol A showed 45% inhibition of MAO (mouse liver) at 5.0 x 10(-6) g/ml, and lemuninols B and C and a naphthoquinone (9) indicated weak activity. Some related quinones were also tested for their MAO inhibitory activities.

Matched MeSH terms: Naphthoquinones/pharmacology
Fulltext Targeted Isolation of Anti-Trypanosomal Naphthofuran-Quinone Compounds from the Mangrove Plant Avicennia lanata

Mazlan NW, Clements C, Edrada-Ebel R

Mar Drugs, 2020 Dec 21;18(12).
PMID: 33371387 DOI: 10.3390/md18120661

The discovery of new secondary metabolites from natural origins has become more challenging in natural products research. Different approaches have been applied to target the isolation of new bioactive metabolites from plant extracts. In this study, bioactive natural products were isolated from the crude organic extract of the mangrove plant Avicennia lanata collected from the east coast of Peninsular Malaysia in the Setiu Wetlands, Terengganu, using HRESI-LCMS-based metabolomics-guided isolation and fractionation. Isolation work on the crude extract A. lanata used high-throughput chromatographic techniques to give two new naphthofuranquinone derivatives, hydroxyavicenol C (1) and glycosemiquinone (2), along with the known compounds avicenol C (3), avicequinone C (4), glycoquinone (5), taraxerone (6), taraxerol (7), β-sitosterol (8) and stigmasterol (9). The elucidation and identification of the targeted bioactive compounds used 1D and 2D-NMR and mass spectrometry. Except for 6-9, all isolated naphthoquinone compounds (1-5) from the mangrove plant A. lanata showed significant anti-trypanosomal activity on Trypanosoma brucei brucei with MIC values of 3.12-12.5 μM. Preliminary cytotoxicity screening against normal prostate cells (PNT2A) was also performed. All compounds exhibited low cytotoxicity, with compounds 3 and 4 showing moderate cytotoxicity of 78.3% and 68.6% of the control values at 100 μg/mL, respectively.

Matched MeSH terms: Naphthoquinones/pharmacology
Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition

Sharma G, Vasanth Kumar S, Wahab HA

J Biomol Struct Dyn, 2018 01;36(1):233-242.
PMID: 28013578 DOI: 10.1080/07391102.2016.1274271

A series of dimeric naphthoquinones containing natural 2-hydroxy-1-4-naphthoquinone moiety was designed, synthesized, and evaluated against neuraminidase of H5N1 virus. p-hydroxy derivatives showed higher inhibition when compared to p-halogenated compounds. Molecular docking studies conducted with H5N1 neuraminidase clearly demonstrated different binding modes of the most active compound onto the open and closed conformations of loop 150. The results thus provide not only evidences of a novel scaffold evaluated as inhibitor, but also a rational explanation involving molecular modeling and the role of loop 150 in the binding.

Matched MeSH terms: Naphthoquinones/pharmacology
Synergistic Antibacterial Activity Between 1,4-Naphthoquinone and β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus

Yap JKY, Tan SYY, Tang SQ, Thien VK, Chan EWL

Microb Drug Resist, 2021 Feb;27(2):234-240.
PMID: 32589487 DOI: 10.1089/mdr.2020.0178

Aims: Currently, limited antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One approach is the use of adjuvants in antibiotic therapy. 1,4-Naphthoquinones are naturally occurring alkaloids shown to have antibacterial properties. The objective of this study is to investigate the synergy between 1,4-naphthoquinone and selected β-lactam antibiotics and to evaluate the potential use of 1,4-naphthoquinone as an adjuvant in antibiotic treatment against MRSA infections. Methods: The antibacterial activity of 1,4-naphthoquinone and plumbagin was tested against nine pathogenic bacterial strains using the microdilution broth method. The interactions between 1,4-naphthoquinone and three antibiotics (cefuroxime, cefotaxime, and imipenem) were estimated by calculating the fractional inhibitory concentration of the combination. Results: The compounds 1,4-naphthoquinone and plumbagin exhibited a broad range of bacteriostatic and bactericidal effects against both Gram-positive and Gram-negative bacteria. The interaction between 1,4-naphthoquinone and imipenem, cefuroxime, and cefotaxime was synergistic against methicillin-sensitive Staphylococcus aureus and MRSA clinical strains. Against ATCC-cultured MRSA, a synergistic effect was observed between 1,4-naphthoquinone and cefotaxime. However, combination with imipenem only produced an additive effect, and an antagonistic action was observed between 1,4-naphthoquinone and cefuroxime. Conclusions: Although individually less potent than common antibiotics, 1,4-naphthoquinone acts synergistically with imipenem, cefuroxime, and cefotaxime against MRSA clinical strains and could potentially be used in adjuvant-antibiotic therapy against multidrug resistant bacteria.

Matched MeSH terms: Naphthoquinones/pharmacology*
Activity of extracts and naphthoquinones from Kigelia pinnata against Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense

Moideen SV, Houghton PJ, Rock P, Croft SL, Aboagye-Nyame F

Planta Med, 1999 Aug;65(6):536-40.
PMID: 10483374

Dichloromethane extracts of the root bark and stem bark of Kigelia pinnata collected from Zimbabwe exhibited antitrypanosomal activity against Trypanosoma brucei brucei in vitro. Activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. The compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). Subsequently, the compounds were assessed for antitrypanosomal activity against T. brucei brucei and T. brucei rhodesiense bloodstream form trypomastigotes in vitro. Compound 1 with a furanonaphthoquinone structure was found to possess pronounced activity against both parasites with IC50 values of 0.12 and 0.045 microM, respectively, although it was less active than the standard drug pentamidine. Compounds 2, 3, and 4 also exhibited activity against the parasites, although to a lesser extent. The activities of the compounds were further assessed by comparison with the cytotoxic activities obtained against KB cell lines.

Matched MeSH terms: Naphthoquinones/pharmacology*
2-Methoxy-1,4-Naphthoquinone (MNQ) suppresses the invasion and migration of a human metastatic breast cancer cell line (MDA-MB-231)

Liew K, Yong PV, Lim YM, Navaratnam V, Ho AS

Toxicol In Vitro, 2014 Apr;28(3):335-9.
PMID: 24291160 DOI: 10.1016/j.tiv.2013.11.008

Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 μM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.

Matched MeSH terms: Naphthoquinones/pharmacology*
Two new naphthoquinone derivatives from the stem bark of Callicarpa maingayi

Asiri SM, Shaari K, Abas F, Al-Mekhlafi NA, Lajis NH

Nat Prod Commun, 2012 Oct;7(10):1333-6.
PMID: 23157003

Two new naphthoquinones designated as 3alpha-hydroxy-2-(2-hydroxypropan-2-yI)-9alpha-methoxy-2,3,3alpha,9alpha-tetra-hydronaphtho[2,3-b]furan-4,9-dione (callicarpa-quinone A, 1) and 5-hydroxy-2-(2-hydroxypropan-2-yl)naphtho[2,3-b]furan-4,9-dione (callicarpaquinone B, 2) were isolated from the chloroform fraction of Callicarpa maingayi. Three other known compounds, identified as avicequinone-C (3), wodeshiol (4) and paulownin (5), were reported for the first time from this species. The structure elucidation of compounds was established by comprehensive 1D and 2D NMR spectroscopic analyses as well as EIMS, UV and IR spectral data. Compounds 1 and 2 were tested in vitro for their cytotoxic activity against human breast cancer MCF-7cells. Compound 2 exhibited strong cytotoxic activity with an IC50 value of 1.9 +/- 0.2 microM, while 1 showed moderate activity with an IC50 value of 25.0 +/- 4.3 microM.

Matched MeSH terms: Naphthoquinones/pharmacology
2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways

Ong JY, Yong PV, Lim YM, Ho AS

Life Sci, 2015 Aug 15;135:158-64.
PMID: 25896662 DOI: 10.1016/j.lfs.2015.03.019

The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.

Matched MeSH terms: Naphthoquinones/pharmacology*
Effects of IL-6, IL-10 and TGF-β on the expression of survivin and apoptosis in nasopharyngeal carcinoma TW01 cells

Poh YW, Gan SY, Tan EL

Exp Oncol, 2012 Jul;34(2):85-9.
PMID: 23013758

The aim of this study is to investigate whether IL-6, IL-10 and TGF-β are able to confer resistance to apoptosis in nasopharyngeal carcinoma cells by upregulating the expression of survivin.

Matched MeSH terms: Naphthoquinones/pharmacology