Displaying publications 41 - 60 of 139 in total

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  1. Lim SH, Mahmood K, Komiyama K, Kam TS
    J Nat Prod, 2008 Jun;71(6):1104-6.
    PMID: 18462006 DOI: 10.1021/np800123g
    A new cycloartane, monocarpinine (1), incorporating a fused tetrahydrofuranyl ring, and a cytotoxic tetracyclic lactam, monomarginine (2), were isolated from a stem bark extract of the Malayan species Monocarpia marginalis. The structures of these compounds were determined using NMR and MS analysis. Monomarginine (2) showed appreciable cytotoxicity toward human KB (both drug-sensitive and drug-resistant) and Jurkat cells.
  2. Lim SH, Sim KM, Abdullah Z, Hiraku O, Hayashi M, Komiyama K, et al.
    J Nat Prod, 2007 Aug;70(8):1380-3.
    PMID: 17608533
    Four new indole alkaloids were obtained from two Kopsia species, 6-oxoleuconoxine (1) from the leaf extract of K. griffithii and kopsinitarine E (2), kopsijasminine (3), and kopsonoline (4) from the stem-bark extract of K. teoi. The structures of these alkaloids were determined using NMR and MS analysis. Kopsijasminine (3) showed moderate activity in reversing multidrug resistance in vincristine-resistant KB cells.
  3. Lim SH, Low YY, Subramaniam G, Abdullah Z, Thomas NF, Kam TS
    Phytochemistry, 2013 Mar;87:148-56.
    PMID: 23200029 DOI: 10.1016/j.phytochem.2012.11.005
    Lumusidines A-D, bisindole alkaloids of the macroline-macroline type, and one of the macroline-pleiocarpamine type, villalstonidine F, were isolated from the stem-bark extract of Alstonia macrophylla (Apocynaceae). The structures and absolute configurations of these alkaloids were established using NMR, MS, and X-ray diffraction analyses.
  4. Nge CE, Chong KW, Thomas NF, Lim SH, Low YY, Kam TS
    J Nat Prod, 2016 05 27;79(5):1388-99.
    PMID: 27077800 DOI: 10.1021/acs.jnatprod.6b00129
    Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.
  5. Wong SP, Chong KW, Lim KH, Lim SH, Low YY, Kam TS
    Org. Lett., 2016 Apr 1;18(7):1618-21.
    PMID: 27033525 DOI: 10.1021/acs.orglett.6b00478
    Two new monoterpene indole alkaloids, characterized by previously unencountered natural product skeletons, viz., arborisidine (1), incorporating indolizidine and cyclohexanone moieties fused to an indole unit, and arbornamine (2), incorporating an unprecedented 6/5/6/5/6 "arbornane" skeleton (distinct from the eburnan or tacaman skeleton), were isolated from a Malayan Kopsia arborea. The structures of the alkaloids were determined based on analysis of the NMR and MS data. Possible biogenetic pathways to these alkaloids from a common pericine precursor (3) are presented.
  6. 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.
  7. 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.
  8. Lim KH, Raja VJ, Bradshaw TD, Lim SH, Low YY, Kam TS
    J Nat Prod, 2015 May 22;78(5):1129-38.
    PMID: 25919190 DOI: 10.1021/acs.jnatprod.5b00117
    Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.
  9. 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.
  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. 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.
  12. 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).
  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. Yeap JS, Tan CH, Yong KT, Lim KH, Lim SH, Low YY, et al.
    Phytochemistry, 2020 Aug;176:112391.
    PMID: 32387883 DOI: 10.1016/j.phytochem.2020.112391
    Fourteen previously undescribed alkaloids comprising two N-1-hydroxymethylmacroline alkaloids, one talpinine-type oxindole acetal, a pair of equilibrating talpinine-type oxindole hemiacetals, eight oxidized derivatives of sarpagine- and akuammiline-type indole alkaloids, in addition to alstochalotine a diastereomer of gelsochalotine recently isolated from Gelsemium elegans, were isolated from the leaf and stem-bark extracts of Alstonia penangiana. The structures and relative configurations of these alkaloids were established using NMR, MS, and in one instance, confirmed by X-ray diffraction analysis. An NMR-based method is described as a useful chemotaxonomic tool for differentiating between A. penangiana and A. macrophylla. Several of the alkaloids isolated showed appreciable growth inhibitory effects when tested against a number of human cancer cell lines.
  15. Chong KW, Yeap JS, Lim SH, Weber JF, Low YY, Kam TS
    J Nat Prod, 2017 11 22;80(11):3014-3024.
    PMID: 29087707 DOI: 10.1021/acs.jnatprod.7b00621
    Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
  16. Lall P, Lim SH, Khairuddin N, Kamarulzaman A
    J Int AIDS Soc, 2015;18(2 Suppl 1):19393.
    PMID: 25724503 DOI: 10.7448/IAS.18.2.19393
    The 50% increase in HIV-related deaths in youth and adolescents (aged 10-24) from 2005 to 2012 highlights the need to improve HIV treatment and care in this population, including treatment adherence and retention. Youth and adolescents from key populations or young key populations (YKP) in particular are highly stigmatized and may face additional barrier(s) in adhering to HIV treatment and services. We reviewed the current knowledge on treatment adherence and retention in HIV care among YKP to identify gaps in the literature and suggest future directions to improve HIV care for YKP.
  17. Lim SH, Bazazi AR, Sim C, Choo M, Altice FL, Kamarulzaman A
    Sex Transm Infect, 2013 Dec;89(8):642-9.
    PMID: 23787168 DOI: 10.1136/sextrans-2012-050995
    OBJECTIVE: To assess the prevalence of unprotected anal intercourse (UAI) and its correlates among ethnic Malay men who have sex with men (MSM).
    METHODS: In 2010, a convenience sample of 350 MSM in Penang were recruited to participate in an anonymous, computerised survey with rapid HIV testing. Participants who were not of Malay ethnicity (n=44) or who did not report sex with another man in the previous 12 months (n=22) were excluded, resulting in 284 participants in the final analysis. Correlates of UAI were examined separately for regular and casual partnerships using bivariate and multivariate logistic regression.
    RESULTS: Four men (1.9%) tested HIV positive. In the past 12 months, 64.7% of participants had regular sexual partners, 77.1% had casual sexual partners and 41.9% had both. Most participants (83.1%) reported UAI, which was more common in regular partnerships. Over two-thirds of participants had never been tested for HIV. In multivariate analysis, agreement about sexual risk reduction practices was associated with a reduction in UAI with regular partners (adjusted OR (AOR)=0.14, 95% CI 0.05 to 0.40). Reporting difficulty in using condoms was associated with an increase in UAI with casual partners (AOR=9.07, 95% CI 3.35 to 24.5), and any exposure to HIV prevention was associated with a decrease in UAI with casual partners (AOR=0.22, 95% CI 0.09 to 0.54).
    CONCLUSIONS: Despite highly prevalent HIV risk behaviours, HIV seropositivity and prior HIV testing were low. Increasing sexual negotiation skills and access to HIV testing and other prevention services may improve future prevention efforts.
    KEYWORDS: HIV; Homosexuality; Prevention; Sexual Behaviour
  18. Shrestha R, Lim SH, Altice FL, Copenhaver M, Wickersham JA, Saifi R, et al.
    J Community Health, 2020 02;45(1):10-19.
    PMID: 31375976 DOI: 10.1007/s10900-019-00713-x
    In settings where stigma and discrimination toward men who have sex with men (MSM) are high or illegal, like in Malaysia, innovative methods to anonymously reach them are urgently needed. The near ubiquitous availability of mobile technology, including smartphones, has the potential to open new frontiers (such as mHealth) to prevent HIV and other sexually transmitted infections (STIs). The extent to which MSM use mHealth tools for HIV and STI prevention in the Malaysia context, however, is unknown. A cross-sectional online survey in 622 Malaysian MSM was conducted between July and November 2017. Participants were recruited via advertisements on mobile apps frequently used by MSM. In addition to demographic, smartphone access and utilization, and other information were assessed using logistic regression to determine factors associated with the use of a smartphone to search for online sexual health information. Nearly all (99.2%) participants owned a smartphone, with 63% reported having used one to seek sexual health information, including HIV/STIs. Overall, 96% used smartphones to find sexual partners, with high levels of HIV risk behavior reported. Independent correlates of smartphone use to seek online sexual health information included older age (aOR 0.943, p = 0.005), higher education (aOR 2.14, p = 027), recent (past year) HIV testing (aOR 3.91, p = 0.026), and seeking sexual partners using geosocial networking apps (aOR 5.58, p = 0.006). These findings suggest high smartphone use by high-risk MSM to seek sexual health information and suggests that mHealth strategies may be an effective strategy to engage MSM in HIV prevention activities.
  19. Earnshaw VA, Cox J, Wong PL, Saifi R, Walters S, Azwa I, et al.
    AIDS Behav, 2023 Jul;27(7):2103-2112.
    PMID: 36472685 DOI: 10.1007/s10461-022-03942-9
    Stigma in healthcare settings is a pernicious barrier to HIV prevention and treatment in contexts with strong HIV-related structural stigma. Previous work has documented substantial stigma towards key populations and people living with HIV (PLWH) among Malaysian doctors. The perspectives of Malaysian key populations and PLWH, however, remain understudied. In 2021, 34 Malaysian participants representing key populations and PLWH engaged in a photovoice study designed to qualitatively explore their experiences with and hopes for doctor interactions. Many participants reported stigma from their doctors, perceiving that doctors view them as not normal, sinful, misguided, and incapable. Several emphasized that they wear figurative masks to conceal aspects of themselves from doctors. Yet, many also remain hopeful for constructive relationships with doctors. They want their doctors to know that they are bright, capable, kind, and valuable. Interventions are needed to address stigma among doctors working in contexts with strong structural stigma.
  20. Lim SH, Lim YC, Zaki RA, Johari BM, Chang CY, Omar SFS, et al.
    PLoS One, 2024;19(4):e0298376.
    PMID: 38626017 DOI: 10.1371/journal.pone.0298376
    BACKGROUND: Post Acute COVID Syndrome (PACS), a complex and poorly understood condition characterised by persistent symptoms following the acute phase of COVID-19 infection, has emerged as a significant global health concern. Healthcare workers who had been at the forefront of the pandemic response are at heightened risk of contracting the virus and subsequently developing PACS. Therefore, we aim to determine the prevalence and risk factors for PACS among healthcare workers infected with COVID-19.

    METHODS: A cross-sectional study was conducted between October 2022 and August 2023 using an online REDCap electronic data capture tool questionnaire. PACS was defined as new or persistent symptoms lasting more than 28 days after a positive SARS-CoV-2 polymerase chain reaction or rapid test kit antigen test. Multivariable logistic regression was performed to determine predictors associated with PACS.

    RESULTS: Among 609 infected healthcare workers, they were predominantly female (71.8%), Malays (84.6%), and aged 18-39 years (70.1%). 50.7% of infected healthcare workers experienced PACS. The most common PACS symptoms experienced were fatigue (27.9%), cough (25.1%), decreased physical strength (20.5%), and musculoskeletal pain (19.2%). Those who are more likely to develop PACS were females, underlying asthma, and COVID-19 severity category 3. On the other hand, those who received booster vaccinations were less likely to develop PACS.

    CONCLUSION: PACS is prevalent among healthcare workers with COVID-19 at the University Malaya Medical Centre. These findings emphasise the critical need for those with higher risk to receive regular health monitoring and checkups to detect any early signs of PACS. It underscores the need for continuous support and healthcare interventions to mitigate the impacts of PACS and ensure the physical and mental well-being of healthcare workers.

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