Displaying all 9 publications

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  1. Mahyudin NA, Blunt JW, Cole AL, Munro MH
    J Biomed Biotechnol, 2012;2012:894708.
    PMID: 22291452 DOI: 10.1155/2012/894708
    The application of an HPLC bioactivity profiling/microtiter plate technique in conjunction with microprobe NMR instrumentation and access to the AntiMarin database has led to the isolation of a new 1. In this example, 1 was isolated from a cytotoxic fraction of an extract obtained from marine-derived Streptomyces sp. cultured on Starch Casein Agar (SCA) medium. The 1D and 2D (1)H NMR and ESIMS data obtained from 20 μg of compound 1 fully defined the structure. The known 2 was also isolated and readily dereplicated using this approach.
  2. Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K
    Anticancer Drugs, 2013 Sep;24(8):852-61.
    PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47
    There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
  3. Hazalin NA, Ramasamy K, Lim SM, Cole AL, Majeed AB
    Phytomedicine, 2012 May 15;19(7):609-17.
    PMID: 22397996 DOI: 10.1016/j.phymed.2012.01.007
    Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis.
  4. Hazalin NA, Ramasamy K, Lim SM, Wahab IA, Cole AL, Abdul Majeed AB
    PMID: 19930582 DOI: 10.1186/1472-6882-9-46
    Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.
  5. van der Sar SA, Blunt JW, Cole AL, Din LB, Munro MH
    J Nat Prod, 2005 Dec;68(12):1799-801.
    PMID: 16378381
    A new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate, was isolated from the fruiting body of a Scleroderma sp. The structure was determined using spectroscopic methods, and an X-ray analysis was carried out for confirmation of the structure. Compound was found to display moderate antimicrobial activity against Bacillus subtilis.
  6. Harun A, Vidyadaran S, Lim SM, Cole AL, Ramasamy K
    PMID: 26047814 DOI: 10.1186/s12906-015-0685-5
    Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines like tumour necrosis factor-alpha (TNF-α) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. This study investigated the protective role of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) against LPS-induced inflammatory events in vitro. These endophytic extracts were previously found to exhibit potent neuroprotective effect against LPS-challenged microglial cells.
  7. Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

  8. Ramasamy K, Lim SM, Abu Bakar H, Ismail N, Ismail MS, Ali MF, et al.
    Phytother Res, 2010 May;24(5):640-3.
    PMID: 19468989 DOI: 10.1002/ptr.2891
    Endophytes, which are receiving increasing attention, have been found to be potential sources of bioactive metabolites following the discovery of paclitaxel producing endophytic fungi. In the present study, a total of 348 endophytes were isolated from different parts of 24 Malaysian medicinal plants. Three selected endophytes (HAB10R12, HAB11R3 and HAB21F25) were investigated for their antimicrobial and cytotoxic activities. For antimicrobial activity, HAB10R12 and HAB11R3 were found to be most active against bacteria and fungi, respectively. Their antimicrobial effects were comparable to, if not better than, a number of current commercial antibacterial and antifungal agents. Both HAB10R12 and HAB21F25 were found to be potential anticancer drug candidates, having potent activity against MCF-7 and HCT116 cell lines and warrant further investigation.
  9. Lang G, Mitova MI, Cole AL, Din LB, Vikineswary S, Abdullah N, et al.
    J Nat Prod, 2006 Oct;69(10):1389-93.
    PMID: 17067148
    Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Malaysian Pterula species. The structures were elucidated by MS and 2D NMR experiments, and the absolute configurations of the constituent amino acids established using Marfey's method. The pterulamides are mainly assembled from nonpolar N-methylated amino acids and, most interestingly, have non-amino-acid N-terminal groups, among them the unusual cinnamoyl, (E)-3-methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl groups. Furthermore, pterulamides I-V are the first natural peptides with a methylamide C-terminus. Pterulamides I and IV are cytotoxic against the P388 cell line with IC50 values of 0.55 and 0.95 microg/mL (0.79 and 1.33 microM), respectively.
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