Displaying publications 61 - 80 of 90 in total

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  1. Sim KS, Sri Nurestri AM, Sinniah SK, Kim KH, Norhanom AW
    Pharmacogn Mag, 2010 Jan;6(21):67-70.
    PMID: 20548939 DOI: 10.4103/0973-1296.59969
    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia.
  2. Muhamad Harish S, Sim KS, Mohd Nor F, Mat Hussin H, Hamzah WM, Najimudin N, et al.
    Genome Announc, 2015;3(6).
    PMID: 26564035 DOI: 10.1128/genomeA.01285-15
    We report here the complete genome sequence of Salmonella enterica subsp. enterica serovar Typhi B/SF/13/03/195 obtained from a typhoid carrier, who is a food handler in Pasir Mas, Kelantan.
  3. Sim DS, Teoh WY, Sim KS, Lim SH, Thomas NF, Low YY, et al.
    J Nat Prod, 2016 Apr 22;79(4):1048-55.
    PMID: 26918761 DOI: 10.1021/acs.jnatprod.5b01117
    Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells.
  4. Halim MA, Rahman AY, Sim KS, Yam HC, Rahim AA, Ghazali AH, et al.
    Genome Announc, 2016;4(1).
    PMID: 26893411 DOI: 10.1128/genomeA.00005-16
    Here, we report the complete genome sequence of Paenibacillus durus type strain ATCC 35681, which can fix atmospheric nitrogen even in the presence of nitrate.
  5. Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.
    PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095
    Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
  6. Yong WK, Sim KS, Poong SW, Wei D, Phang SM, Lim PE
    3 Biotech, 2019 Aug;9(8):315.
    PMID: 31406637 DOI: 10.1007/s13205-019-1848-8
    An ecologically important tropical freshwater microalga, Scenedesmus quadricauda, was exposed to Ni toxicity under two temperature regimes, 25 and 35 °C to investigate the interactive effects of warming and different Ni concentrations (0.1, 1.0 and 10.0 ppm). The stress responses were assessed from the growth, photosynthesis, reactive oxygen species (ROS) generation and metabolomics aspects to understand the effects at both the physiological and biochemical levels. The results showed that the cell densities of the cultures were higher at 35 °C compared to 25 °C, but decreased with increasing Ni concentrations at 35 °C. In terms of photosynthetic efficiency, the maximum quantum yield of photosystem II (Fv/Fm) of S. quadricauda remained consistent across different conditions. Nickel concentration at 10.0 ppm affected the maximum rate of relative electron transport (rETRm) and saturation irradiance for electron transport (Ek) in photosynthesis. At 25 °C, the increase of non-photochemical quenching (NPQ) values in cells exposed to 10.0 ppm Ni might indicate the onset of thermal dissipation process as a self-protection mechanism against Ni toxicity. The combination of warming and Ni toxicity induced a strong oxidative stress response in the cells. The ROS level increased significantly by 40% after exposure to 10.0 ppm of Ni at 35 °C. The amount of Ni accumulated in the biomass was higher at 25 °C compared to 35 °C. Based on the metabolic profile, temperature contributed the most significant differentiation among the samples compared to Ni treatment and the interaction between the two factors. Amino acids, sugars and organic acids were significantly regulated by the combined factors to restore homeostasis. The most affected pathways include sulphur, amino acids, and nitrogen metabolisms. Overall, the results suggest that the inhibitory effect of Ni was lower at 35 °C compared to 25 °C probably due to lower metal uptake and primary metabolism restructuring. The ability of S. quadricauda to accumulate substantial amount of Ni and thrive at 35 °C suggests the potential use of this strain for phycoremediation and outdoor wastewater treatment.
  7. Tan CH, Liew JL, Navanesan S, Sim KS, Tan NH, Tan KY
    PMID: 32742279 DOI: 10.1590/1678-9199-JVATITD-2020-0013
    Background: The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs.

    Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.

    Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.

    Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.

  8. Sim DS, Navanesan S, Sim KS, Gurusamy S, Lim SH, Low YY, et al.
    J Nat Prod, 2019 04 26;82(4):850-858.
    PMID: 30869890 DOI: 10.1021/acs.jnatprod.8b00919
    Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma- Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 μM range.
  9. Navanesan S, Abdul Wahab N, Manickam S, Cheow YL, Sim KS
    Chem Biol Interact, 2017 Aug 01;273:37-47.
    PMID: 28578903 DOI: 10.1016/j.cbi.2017.05.022
    The active isolate of LF1 in Leptospermum javanicum was further looked into its capabilities in provoking an apoptotic reaction and suppressing the metastasis process in treated non-small lung cancer cells. LF1 underwent isolation and purification to yield a white powder which was identified as Betulinic acid (BA) via NMR, LCMS and IR spectroscopy. The isolate, BA, which produced an encouraging cytotoxic effect against non-small lung cancer cells (A549 and NCI-H1299) through the MTT assay, was further assessed with TUNEL, Sub-G1 population quantification, acridine orange/ethidium bromide staining as well as activated caspase-3 detection. The results pointed towards the induction of apoptosis as a result of increasing doses of BA, regardless of the p53 status in both cell lines. Treatment with BA also prevented an effective attachment of the invasive A549 cells onto a new culture surface in addition to diminishing the migratory potential of treated cells across a porous membrane. Further investigation through the ELISA detection and gelatin zymography showed an adverse effect to production of matrix metalloproteinase-2 (MMP-2) while the levels of matrix metalloproteinase-9 (MMP-9) were not negatively affected. The findings from this study validate the potential of L. javanicum as a potential anti-cancer treatment as stated in our previous study. The isolate, BA not only showed a capacity in inducing apoptotic cell death in non-small lung cancer cells, but managed to distort the ability of the cancer cells in effectively undergoing the metastasis process.
  10. Tan CH, Yeap JS, Lim SH, Low YY, Sim KS, Kam TS
    J Nat Prod, 2021 05 28;84(5):1524-1533.
    PMID: 33872002 DOI: 10.1021/acs.jnatprod.1c00013
    A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (2). Compounds 1 and 2 showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. In particular, the two compounds showed potent and selective antiproliferative activity against HT-29 cells, as well as strong growth inhibitory effects against HT-29 spheroids. Cell death mechanistic studies revealed that the compounds induced mitochondrial apoptosis and G0/G1 cell cycle arrest in HT-29 cells in a time-dependent manner, while in vitro tubulin polymerization assays and molecular docking analysis showed that the compounds are microtubule-stabilizing agents, which are predicted to bind at the β-tubulin subunit at the Taxol-binding site.
  11. Chan WC, Saad HM, Sim KS, Lee VS, Ang CW, Yeong KY, et al.
    PMID: 34198119 DOI: 10.1016/j.saa.2021.120099
    A new chemosensor 1 was synthesized by reacting rhodamine B hydrazide and 2,3,4-trihydroxybenzaldehyde, which was then characterized by spectroscopic techniques and single crystal X-ray crystallography. Sensor 1 has the ability to sense Co2+/Cu2+ ions by "naked-eye" with an apparent colour change from colourless to pink in different solvent system, MeCN and DMF respectively. Furthermore, it can selectively detect Co2+/Cu2+ among wide range of different metal ions, and it exhibits low detection limit of 4.425 × 10-8 M and 1.398 × 10-7 M respectively. Binding mode of the two complexes were determined to be 1:1 stoichiometry for Co2+ complex and 1:2 stoichiometry for Cu2+ complex through Job's plot, IR spectroscopy, mass spectrometry and 1H NMR spectroscopy. Moreover, reversibility of the sensor 1 as copper (II) ion detector was determined by using EDTA and the results showed that sensor 1 can be reused for at least 6 cycles. Other than that, a low cost chemosensor test strips were fabricated for the convenient "naked-eye" detection of Co2+ and Cu2+ in pure aqueous media. The MTT assay was conducted in order to determine the cytotoxicity of sensor 1 towards human cell lines.
  12. Nge CE, Sim KS, Lim SH, Thomas NF, Low YY, Kam TS
    J Nat Prod, 2016 10 28;79(10):2709-2717.
    PMID: 27759387
    Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.
  13. Wong SK, Wong SP, Sim KS, Lim SH, Low YY, Kam TS
    J Nat Prod, 2019 07 26;82(7):1902-1907.
    PMID: 31241923 DOI: 10.1021/acs.jnatprod.9b00255
    Three new alkaloids were isolated from the bark extract of the Malayan Kopsia arborea, viz., arbophyllidine (1), an unusual pentacyclic, monoterpenoid indole characterized by an absence of oxygen atoms and incorporating a new carbon-nitrogen skeleton, and arbophyllinines A (2) and B (3), two pentacyclic corynanthean alkaloids incorporating a hydroxyethyl-substituted tetrahydrofuranone ring. The structures of the alkaloids were deduced based on analysis of the MS and NMR data and confirmed by X-ray diffraction analyses. The absolute configuration of arbophyllidine (1) was established based on experimental and calculated ECD data, while that of arbophyllinine A was based on X-ray diffraction analysis (Cu Kα). A reasonable biosynthetic route to arbophyllidine (1) from a pericine precursor is presented. Arbophyllidine (1) showed pronounced in vitro growth inhibitory activity against the HT-29 human cancer cell line with IC50 6.2 μM.
  14. Sim KS, Kho YY, Tso CP, Nia ME, Ting HY
    Scanning, 2013 Mar-Apr;35(2):75-87.
    PMID: 22777599 DOI: 10.1002/sca.21037
    Detection of cracks from stainless steel pipe images is done using contrast stretching technique. The technique is based on an image filter technique through mathematical morphology that can expose the cracks. The cracks are highlighted and noise removal is done efficiently while still retaining the edges. An automated crack detection system with a camera platform has been successfully implemented. We compare crack extraction in terms of quality measures with those of Otsu's threshold technique and the another technique (Iyer and Sinha, 2005). The algorithm shown is able to achieve good results and perform better than these other techniques.
  15. Tang SY, Tan CH, Sim KS, Yong KT, Lim KH, Low YY, et al.
    Phytochemistry, 2023 Apr;208:113587.
    PMID: 36646163 DOI: 10.1016/j.phytochem.2023.113587
    Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.
  16. Sim KS, Chong SS, Tso CP, Nia ME, Chong AK, Abbas SF
    Springerplus, 2014;3:268.
    PMID: 25045606 DOI: 10.1186/2193-1801-3-268
    Data analysis based on breast cancer risk factors such as age, race, breastfeeding, hormone replacement therapy, family history, and obesity was conducted on breast cancer patients using a new enhanced computerized database management system. My Structural Query Language (MySQL) is selected as the application for database management system to store the patient data collected from hospitals in Malaysia. An automatic calculation tool is embedded in this system to assist the data analysis. The results are plotted automatically and a user-friendly graphical user interface is developed that can control the MySQL database. Case studies show breast cancer incidence rate is highest among Malay women, followed by Chinese and Indian. The peak age for breast cancer incidence is from 50 to 59 years old. Results suggest that the chance of developing breast cancer is increased in older women, and reduced with breastfeeding practice. The weight status might affect the breast cancer risk differently. Additional studies are needed to confirm these findings.
  17. Teoh WY, Sim KS, Moses Richardson JS, Abdul Wahab N, Hoe SZ
    PMID: 24369485 DOI: 10.1155/2013/958407
    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
  18. Lim JL, Sim KS, Yong KT, Loong BJ, Ting KN, Lim SH, et al.
    Phytochemistry, 2015 Sep;117:317-24.
    PMID: 26125941 DOI: 10.1016/j.phytochem.2015.06.024
    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.
  19. Yeap JS, Saad HM, Tan CH, Sim KS, Lim SH, Low YY, et al.
    J Nat Prod, 2019 11 22;82(11):3121-3132.
    PMID: 31642315 DOI: 10.1021/acs.jnatprod.9b00712
    A methanol extract of the stem bark of the Malayan Alstonia penangiana provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, 1-6) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, 7). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (1-6) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC50 values: 0.02-9.0 μM).
  20. Chua RAHW, Lim SK, Chee CF, Chin SP, Kiew LV, Sim KS, et al.
    Eur Rev Med Pharmacol Sci, 2022 Feb;26(3):828-845.
    PMID: 35179749 DOI: 10.26355/eurrev_202202_27991
    Sutures are used to facilitate wound healing and play an important role in ensuring the success of surgical interventions in healthcare facilities. Suture-associated surgical site infection (SSI) may develop when bacterial contaminants colonize the suture surface and establish biofilms that are highly resistant to antibiotic treatment. The outcome of SSI affects postoperative care, leading to high rates of morbidity and mortality, prolonged hospitalization, and increased financial burden. Antimicrobial sutures coated with antiseptics such as triclosan and chlorhexidine have been used to minimize the occurrence of SSI. However, as the efficacy of antiseptic-based sutures may be affected due to the emergence of resistant strains, new approaches for the development of alternative antimicrobial sutures are necessary. This review provides an update and outlook of various approaches in the design and development of antimicrobial sutures. Attaining a zero SSI rate will be possible with the advancement in suturing technology and implementation of good infection control practice in clinical settings.
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