MyMedR

Displaying publications 81 - 86 of 86 in total

Abstract:

Sort:

Acylphenols and dimeric acylphenols from Myristica maxima Warb

Othman MA, Sivasothy Y, Looi CY, Ablat A, Mohamad J, Litaudon M, et al.

Fitoterapia, 2016 Jun;111:12-7.
PMID: 27072985 DOI: 10.1016/j.fitote.2016.04.004

Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity.
Fulltext A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma

Dai X, Wang L, Deivasigamni A, Looi CY, Karthikeyan C, Trivedi P, et al.

Oncotarget, 2017 Feb 21;8(8):12831-12842.
PMID: 28086233 DOI: 10.18632/oncotarget.14606

A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells.
Fulltext A cell-based screening system for anti-influenza A virus agents

Wong WY, Loh SW, Ng WL, Tan MC, Yeo KS, Looi CY, et al.

Sci Rep, 2015;5:8672.
PMID: 25728279 DOI: 10.1038/srep08672

Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
Fulltext A Systematic Review of Molecular Hydrogen Therapy in Cancer Management

Mohd Noor MNZ, Alauddin AS, Wong YH, Looi CY, Wong EH, Madhavan P, et al.

Asian Pac J Cancer Prev, 2023 Jan 01;24(1):37-47.
PMID: 36708550 DOI: 10.31557/APJCP.2023.24.1.37

BACKGROUND: Cancer remains a challenging target to cure, with present therapeutic methods unable to exhibit restorative outcomes without causing severe negative effects. Molecular hydrogen (H2) has been reported to be a promising adjunctive therapy for cancer treatment, having the capability to induce anti-proliferative, anti-oxidative, pro-apoptotic and anti-tumoural effects. This review summarises the findings from various articles on the mechanism, treatment outcomes, and overall effectiveness of H2 therapy on cancer management.
METHODS: Using Cochrane, PubMed, and Google Scholar as the search engines, full-text articles in the scope of the study, written in English and within 10 years of publication were selected.
RESULTS: Out of the 677 articles, 27 articles fulfilled the eligibility criteria, where data was compiled into a table, outlining the general characteristics and findings. Throughout the different forms of H2 administration, study design and types of cancers reported, outcomes were found to be consistent.
CONCLUSION: From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy.
Fulltext A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway

Hajrezaie M, Paydar M, Moghadamtousi SZ, Hassandarvish P, Gwaram NS, Zahedifard M, et al.

ScientificWorldJournal, 2014;2014:540463.
PMID: 24737979 DOI: 10.1155/2014/540463

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
Fulltext (6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells

Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.

PLoS One, 2015;10(5):e0126126.
PMID: 25946039 DOI: 10.1371/journal.pone.0126126

Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.