Displaying publications 41 - 60 of 139 in total

Abstract:
Sort:
  1. Fulltext Group sex, suicidality and online partners: implications for HIV and suicide prevention: a short report
    Kongjareon Y, Samoh N, Lim SH, Peerawaranun P, Jonas KJ, Guadamuz TE
    AIDS Care, 2020 08;32(8):954-958.
    PMID: 32160793 DOI: 10.1080/09540121.2020.1734174
    HIV-related factors and suicide-risk status were assessed among YMSM aged 18-24 years recruited through various MSM-related online social apps in Bangkok (N = 1394). The online survey assessed demographic characteristics, sexual behaviours and suicide-risk status. Measure of suicide risk was taken from the Suicidal Behaviors Questionnaire-Revised (cut-off score of seven or higher). Among participants, 249 (17.9%) reported suicide-risk. In multivariable logistic regression, correlates of suicide-risk status included having sometimes or often ever participated in group sex (AOR=1.58, 95% CI: 1.17-2.14), having received money or opportunities for sex (AOR=1.54, 95% CI: 1.09-2.17), often seeking partners online (AOR=1.59, 95% CI: 1.05-2.39), inconsistent condom use (AOR=1.67, 95% CI: 1.26-2.21), and self-assessed as having "medium" or "high" HIV risk (AOR=2.53, 95% CI: 1.61-3.98 and AOR=3.35, 95% CI: 1.92-5.82, respectively). Findings suggest that HIV risk behaviours shown by YMSM are significantly associated with higher risk of suicide.
  2. Alstoscholactine and Alstolaxepine, Monoterpenoid Indole Alkaloids with γ-Lactone-Bridged Cycloheptane and Oxepane Moieties from Alstonia scholaris
    Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
  3. A randomized double blind control trial comparing filgrastim and pegfilgrastim in cyclophosphamide peripheral blood hematopoietic stem cell mobilization
    Kuan JW, Su AT, Wong SP, Sim XY, Toh SG, Ong TC, et al.
    Transfus Apher Sci, 2015 Oct;53(2):196-204.
    PMID: 25910537 DOI: 10.1016/j.transci.2015.03.017
    There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.
  4. Fulltext Research priorities in epilepsy for the Asia-Oceanian region
    Kwan P, Cabral-Lim L, D'Souza W, Jain S, Lee BI, Liao W, et al.
    Epilepsia, 2015 May;56(5):667-73.
    PMID: 25823580 DOI: 10.1111/epi.12957
    The Asia-Oceanian region is the most populous region in the world. Although there has been substantial economic development and improvement in health services in recent years, epilepsy remains generally an underrecognized and understudied condition. To help promote research in the region, the Commission on Asian and Oceanian Affairs (CAOA) of the International League Against Epilepsy (ILAE) appointed the Research Task Force (RTF) to facilitate the development of research priorities for the region. Research that focuses on issues that are unique or of particular importance in the Asia-Oceanian region is encouraged, and that captures the impact of the dynamic socioeconomic changes taking place in the region is emphasized. Based on these considerations, we propose research "dimensions" as priorities within the Asia-Oceanian region. These are studies (1) that would lead to fuller appreciation of the health burden of epilepsy, particularly the treatment gap; (2) that would lead to better understanding of the causes of epilepsy; (3) that would alleviate the psychosocial consequences of epilepsy; (4) that would develop better therapies and improved therapeutic outcomes; and (5) that would improve the research infrastructure.
  5. Fulltext Review: an urgent need for research on factors impacting adherence to and retention in care among HIV-positive youth and adolescents from key populations
    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.
  6. Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population
    Lee YL, Zaini AA, Idris AN, Abdullah RA, Wong JS, Hong JS, et al.
    J Paediatr Child Health, 2023 Jul;59(7):879-884.
    PMID: 37066819 DOI: 10.1111/jpc.16405
    AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls.

    METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records.

    RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood.

    CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

  7. Discovering the Potentials of Medicinal Mushrooms in Combating Depression - A Review
    Lew SY, Teoh SL, Lim SH, Lim LW, Wong KH
    Mini Rev Med Chem, 2020;20(15):1518-1531.
    PMID: 32452327 DOI: 10.2174/1389557520666200526125534
    Depression is the most common form of mental illness and the major cause of disability worldwide. Symptoms of depression, including feelings of intense sadness and hopelessness, may occur after a specific event or in response to a gradual decline in health and functional status, often associated with aging. Current therapies for treating these symptoms include antidepressant drugs, counseling and behavioral therapy. However, antidepressant drugs are associated with mild to severe adverse effects, which has prompted the need for better treatment options. Medicinal mushrooms are valuable sources of food and medicine and are increasingly being used as supplements or as alternative medicines in standard healthcare. Numerous studies have provided insights into the neuroprotective effects of medicinal mushrooms, which are attributed to their antioxidant, anti-neuroinflammatory, cholinesterase inhibitory and neuroprotective properties. In this review, we comprehensively examine the role of these medicinal mushrooms in the treatment of depression. However, to apply these natural products in clinical settings, the therapeutic agent needs to be properly evaluated, including the active ingredients, the presence of synergistic effects, efficient extraction methods, and stabilization of the active ingredients for delivery into the body as well as crossing the blood-brain barrier.
  8. Fulltext Neuroprotective effects of Hericium erinaceus (Bull.: Fr.) Pers. against high-dose corticosterone-induced oxidative stress in PC-12 cells
    Lew SY, Lim SH, Lim LW, Wong KH
    BMC Complement Med Ther, 2020 Nov 11;20(1):340.
    PMID: 33176761 DOI: 10.1186/s12906-020-03132-x
    BACKGROUND: Hericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression.

    METHODS: PC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis.

    RESULTS: We observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE.

    CONCLUSIONS: HESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.

  9. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety
    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.
  10. Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety
    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.
  11. Fulltext Outcome after neoadjuvant chemotherapy in Asian breast cancer patients
    Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
  12. Fulltext Rosamines targeting the cancer oxidative phosphorylation pathway
    Lim SH, Wu L, Kiew LV, Chung LY, Burgess K, Lee HB
    PLoS One, 2014;9(3):e82934.
    PMID: 24622277 DOI: 10.1371/journal.pone.0082934
    Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.
  13. Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla
    Lim SH, Low YY, Sinniah SK, Yong KT, Sim KS, Kam TS
    Phytochemistry, 2014 Feb;98:204-15.
    PMID: 24342109 DOI: 10.1016/j.phytochem.2013.11.014
    A total of seventeen alkaloids, comprising six macroline (including alstofolinine A, a macroline indole incorporating a butyrolactone ring-E), two ajmaline, one sarpagine, and eight akuammiline alkaloids, were isolated from the stem-bark and leaf extracts of the Malayan Alstonia macrophylla. The structure and relative configurations of these alkaloids were established using NMR, MS and in several instances, confirmed by X-ray diffraction analysis. Six of these alkaloids were effective in reversing multidrug-resistance (MDR) in vincristine-resistant KB cells.
  14. High rates of unprotected anal intercourse with regular and casual partners and associated risk factors in a sample of ethnic Malay men who have sex with men (MSM) in Penang, Malaysia
    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
  15. Perhentidines A-C: macroline-macroline bisindoles from Alstonia and the absolute configuration of perhentinine and macralstonine
    Lim SH, Low YY, Tan SJ, Lim KH, Thomas NF, Kam TS
    J Nat Prod, 2012 May 25;75(5):942-50.
    PMID: 22559995 DOI: 10.1021/np300120p
    Three new bisindole alkaloids of the macroline-macroline type, perhentidines A-C (1-3), were isolated from the stem-bark extract of Alstonia macrophylla and Alstonia angustifolia. The structures of these alkaloids were established on the basis of NMR and MS analyses. The absolute configurations of perhentinine (4) and macralstonine (5) were established by X-ray diffraction analyses, which facilitated assignment of the configuration at C-20 in the regioisomeric bisindole alkaloids perhentidines A-C (1-3). A potentially useful method for the determination of the configuration at C-20 based on comparison of the NMR chemical shifts of the bisindoles and their acetate derivatives, in these and related bisindoles with similar constitution and branching of the monomeric units, is also presented.
  16. Factors associated with unprotected receptive anal intercourse with internal ejaculation among men who have sex with men in a large Internet sample from Asia
    Lim SH, Guadamuz TE, Wei C, Chan R, Koe S
    AIDS Behav, 2012 Oct;16(7):1979-87.
    PMID: 22714116
    We examined socio-demographic and behavioral characteristics of men who have sex with men (MSM) residing in Asia and correlates of unprotected receptive intercourse with Internet ejaculation (URAIE). Asia Internet MSM Sex Survey, a behavioral survey of MSM in Asia was conducted from 1 January to 28 February 2010. Data analysis was limited to participants aged 18 or above, biological male, and had one regular or casual sex partner in the past 6 months (n = 10,413). Pearson's Chi-square test, t test and logistic regression were used to examine the correlates of URAIE in the past 6 months, the highest risk sexual behavior sampled. Of 7311 participants who had receptive anal intercourse, 47.5 % had URAIE, which was associated with the following attributes: less than high-school education and pre-college education compared to university (AOR = 1.53, 95 % CI: 1.28, 1.83; AOR = 1.22, CI: 1.08, 1.37), being in the heterosexual marriage (AOR = 1.35, CI: 1.18, 1.56), having regular partners or both regular and casual partners compared to having casual partners (AOR = 2.85, CI: 2.48, 3.27; AOR = 2.32, CI: 2.06, 2.62), HIV-positive compared to HIV-negative status (AOR = 1.39, 95 % CI: 1.08, 1.81), higher perception of HIV risk (AOR = 1.62, CI: 1.34, 1.95), use of recreational drug before sex (AOR = 1.30, CI: 1.14, 1.49), and use of the Internet as the main way to seek sex partners (AOR = 1.21, CI: 1.08, 1.36). MSM from certain Asian countries reported alarming rates of URAIE. The internet can be used as a platform for HIV surveillance and intervention.
  17. Lumutinines A-D, linearly fused macroline-macroline and macroline-sarpagine bisindoles from Alstonia macrophylla
    Lim SH, Tan SJ, Low YY, Kam TS
    J Nat Prod, 2011 Dec 27;74(12):2556-62.
    PMID: 22148233 DOI: 10.1021/np200730j
    Four new linearly fused bisindole alkaloids, lumutinines A-D (1-4), were isolated from the stem-bark extract of Alstonia macrophylla. Lumutinines A (1) and B (2) represent the first examples of linear, ring A/F-fused macroline-macroline-type bisindoles, while lumutinines C (3) and D (4) were constituted from the union of macroline and sarpagine moieties. A reinvestigation of the stereochemical assignment of alstoumerine (8) by NMR and X-ray diffraction analyses indicated that the configuration at C-16 and C-19 required revision.
  18. Glycosylation is not necessary for recognition of the fusion glycoprotein domain of the human respiratory syncytial virus by a polyclonal antibody
    Lim SH, Jahanshiri F, Jalilian FA, Rahim RA, Sekawi Z, Yusoff K
    Acta Virol., 2010;54(3):181-7.
    PMID: 20822310
    Human respiratory syncytial virus (HRSV) is a leading pathogen causing lower respiratory tract infections in infants and young children worldwide. In line with the development of an effective vaccine against HRSV, a domain of the fusion (F) glycoprotein of HRSV was produced and its immunogenicity and antigenic properties, namely the effect of deficient glycosylation was examined. A His-tagged recombinant F (rF) protein was expressed in Escherichia coli, solubilized with 8 mol/l urea, purified by the Ni-NTA affinity chromatography and used for the raising of a polyclonal antibody in rabbits. The non-glycosylated rF protein proved to be a strong immunogen that induced a polyclonal antibody that was able to recognize also the glycosylated F1 subunit of native HRSV. The other way around, a polyclonal antibody prepared against the native HRSV was able to react with the rF protein. These results indicated that glycosylation was not necessary for the F domain aa 212-574 in order to be recognized by the specific polyclonal antibody.
  19. In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy
    Lim SH, Thivierge C, Nowak-Sliwinska P, Han J, van den Bergh H, Wagnières G, et al.
    J Med Chem, 2010 Apr 8;53(7):2865-74.
    PMID: 20199028 DOI: 10.1021/jm901823u
    To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.
  20. New cytotoxic rosamine derivatives selectively accumulate in the mitochondria of cancer cells
    Lim SH, Wu L, Burgess K, Lee HB
    Anticancer Drugs, 2009 Jul;20(6):461-8.
    PMID: 19387338 DOI: 10.1097/CAD.0b013e32832b7bee
    Conventional cytotoxic anticancer drugs that target all rapidly dividing cells are nonselective in their mechanism of action, because they disrupt essential components that are crucial to both malignant and proliferating normal cells. Instead, targeting cellular functions that are distinctly different between normal and cancer cells may provide a basis for selective killing of tumor cells. One such strategy that is still largely unexplored is to utilize the relatively higher negative mitochondrial membrane potential in carcinoma cells compared with adjacent normal epithelial cells to enhance accumulation and retention of cytotoxic lipophilic cations in the former. In this study, the anticancer activities of a new class of rosamines with cyclic amine substituents and their structure-activity relationships were investigated. From an in-vitro cell growth inhibition assay, 14 of the rosamines inhibited the growth of human leukemia HL-60 cells by 50% at micromolar or lower concentrations. Derivatives containing hydrophilic substituents had less potent activity, whereas aryl substitution at the meso position conferred extra activity with thiofuran and para-iodo aryl substitutions being the most potent. In addition, both compounds were at least 10-fold more cytotoxic than rhodamine 123 against a panel of cell lines of different tissue origin and similar to rhodamine 123, exhibited more cytotoxicity against cancer cells compared with immortalized normal epithelial cells of the same organ type. In subsequent experiments, the para-iodo aryl substituted rosamine was found to localize exclusively within the mitochondria and induced apoptosis as the major mode of cell death. Our results suggest that these compounds offer potential for the design of mitochondria-targeting agents that either directly kill or deliver cytotoxic drugs to selectively kill cancer cells.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links