Displaying publications 61 - 80 of 146 in total

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  1. Criofolinine and vernavosine, new pentacyclic indole alkaloids incorporating pyrroloazepine and pyridopyrimidine moieties derived from a common yohimbine precursor
    Nge CE, Gan CY, Lim KH, Ting KN, Low YY, Kam TS
    Org. Lett., 2014 Dec 19;16(24):6330-3.
    PMID: 25454201 DOI: 10.1021/ol503072g
    Two new indole alkaloids characterized by previously unencountered natural product skeletons, viz., criofolinine (1), incorporating a pyrroloazepine motif within a pentacyclic ring system, and vernavosine (2, isolated as its ethyl ether derivative 3, which on hydrolysis regenerated the putative precursor alkaloid 2), incorporating a pyridopyrimidine moiety embedded within a pentacyclic carbon framework, were isolated from a Malayan Tabernaemontana species. The structures and absolute configuration of these alkaloids were determined on the basis of NMR and MS analysis and confirmed by X-ray diffraction analysis.
  2. Fulltext Reversal of ampicillin resistance in MRSA via inhibition of penicillin-binding protein 2a by Acalypha wilkesiana
    Santiago C, Pang EL, Lim KH, Loh HS, Ting KN
    Biomed Res Int, 2014;2014:965348.
    PMID: 25101303 DOI: 10.1155/2014/965348
    The inhibitory activity of a semipure fraction from the plant, Acalypha wilkesiana assigned as 9EA-FC-B, alone and in combination with ampicillin, was studied against methicillin-resistant Staphylococcus aureus (MRSA). In addition, effects of the combination treatment on PBP2a expression were investigated. Microdilution assay was used to determine the minimal inhibitory concentrations (MIC). Synergistic effects of 9EA-FC-B with ampicillin were determined using the fractional inhibitory concentration (FIC) index and kinetic growth curve assay. Western blot experiments were carried out to study the PBP2a expression in treated MRSA cultures. The results showed a synergistic effect between ampicillin and 9EA-FC-B treatment with the lowest FIC index of 0.19 (synergism ≤ 0.5). The presence of 9EA-FC-B reduced the MIC of ampicillin from 50 to 1.56 μg mL(-1). When ampicillin and 9EA-FC-B were combined at subinhibitory level, the kinetic growth curves were suppressed. The antibacterial effect of 9EA-FC-B and ampicillin was shown to be synergistic. The synergism is due the ability of 9EA-FC-B to suppress the activity of PBP2a, thus restoring the susceptibility of MRSA to ampicillin. Corilagin was postulated to be the constituent responsible for the synergistic activity showed by 9EA-FC-B.
  3. Fulltext Prevalence, awareness, treatment and control of diabetes mellitus among the elderly: The 2011 National Health and Morbidity Survey, Malaysia
    Ho BK, Jasvindar K, Gurpreet K, Ambigga D, Suthahar A, Cheong SM, et al.
    Malays Fam Physician, 2014;9(3):12-9.
    PMID: 26425300 MyJurnal
    Diabetes mellitus is an important cardiovascular risk factor. The objective of this study was to provide population-based estimates on the prevalence, awareness, treatment and control rate of diabetes among the older persons in Malaysia. Analysis of secondary data from a cross-sectional national population-based survey was done, which was conducted in 2011 throughout Malaysia. A total of 2764 respondents (15.5%) were older persons. The overall prevalence of diabetes among older persons was 34.4% in which 65.2% were aware of their diabetes status. Out of those who were aware, 87.5% had been treated. Only 21.8% of those treated had their diabetes controlled. The results of multiple logistic regression showed that the factors associated with higher awareness rates were women, Indians and higher income groups; factors associated with higher treatment rates were urban residents and those who were married and widow/widower/ divorcee. There was a high overall prevalence, awareness and treatment rate of diabetes among older persons in Malaysia but with suboptimal control rate.
    Study name: National Health and Morbidity Survey (NHMS-2011)
  4. Hispidacine, an unusual 8,4'-oxyneolignan-alkaloid with vasorelaxant activity, and hispiloscine, an antiproliferative phenanthroindolizidine alkaloid, from Ficus hispida Linn
    Yap VA, Loong BJ, Ting KN, Loh SH, Yong KT, Low YY, et al.
    Phytochemistry, 2015 Jan;109:96-102.
    PMID: 25468714 DOI: 10.1016/j.phytochem.2014.10.032
    Hispidacine, an 8,4'-oxyneolignan featuring incorporation of an unusual 2-hydroxyethylamine moiety at C-7, and hispiloscine, a phenanthroindolizidine alkaloid, were isolated from the stem-bark and leaves of the Malaysian Ficus hispida Linn. Their structures were established by spectroscopic analysis. Hispidacine induced a moderate vasorelaxant activity in rat isolated aorta, while hispiloscine showed appreciable antiproliferative activities against MDA-MB-231, MCF-7, A549, HCT-116 and MRC-5 cell lines.
  5. Fulltext Inhibitory effect of Duabanga grandiflora on MRSA biofilm formation via prevention of cell-surface attachment and PBP2a production
    Santiago C, Lim KH, Loh HS, Ting KN
    Molecules, 2015 Mar 10;20(3):4473-82.
    PMID: 25764489 DOI: 10.3390/molecules20034473
    Formation of biofilms is a major factor for nosocomial infections associated with methicillin-resistance Staphylococcus aureus (MRSA). This study was carried out to determine the ability of a fraction, F-10, derived from the plant Duabanga grandiflora to inhibit MRSA biofilm formation. Inhibition of biofilm production and microtiter attachment assays were employed to study the anti-biofilm activity of F-10, while latex agglutination test was performed to study the influence of F-10 on penicillin-binding protein 2a (PBP2a) level in MRSA biofilm. PBP2a is a protein that confers resistance to beta-lactam antibiotics. The results showed that, F-10 at minimum inhibitory concentration (MIC, 0.75 mg/mL) inhibited biofilm production by 66.10%; inhibited cell-surface attachment by more than 95%; and a reduced PBP2a level in the MRSA biofilm was observed. Although ampicilin was more effective in inhibiting biofilm production (MIC of 0.05 mg/mL, 84.49%) compared to F-10, the antibiotic was less effective in preventing cell-surface attachment. A higher level of PBP2a was detected in ampicillin-treated MRSA showing the development of further resistance in these colonies. This study has shown that F-10 possesses anti-biofilm activity, which can be attributed to its ability to reduce cell-surface attachment and attenuate the level of PBP2a that we postulated to play a crucial role in mediating biofilm formation.
  6. Predictors of physical inactivity among elderly malaysians: recommendations for policy planning
    Kaur J, Kaur G, Ho BK, Yao WK, Salleh M, Lim KH
    Asia Pac J Public Health, 2015 Apr;27(3):314-22.
    PMID: 24425796 DOI: 10.1177/1010539513517257
    Physical inactivity is the fourth leading risk factor for global mortality. Regular moderate-intensity physical activity has significant benefits for health. To determine the socioeconomic predictors of physical inactivity among elderly Malaysian population. A nationwide community-based survey was conducted among 4831 respondents aged ≥60 years with a face-to-face questionnaire. The prevalence of physical inactivity among the elderly was 88.0%, highest in respondents aged older than 80 years (95.4%), females (90.1%), other Bumiputra (92.2%), earning household income less than RM1000 (87.9%), and residing in urban locality (88.4%). In the multivariate model, the predictors of physical inactivity were only sex, ethnicity, locality, and age group (adjusted odds ratio = 1.3-3.6). The predictors of physical inactivity can identify the risk factors to develop policies that will reduce the public health burden of noncommunicable diseases.
  7. 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.
  8. Arboridinine, a Pentacyclic Indole Alkaloid with a New Cage Carbon-Nitrogen Skeleton Derived from a Pericine Precursor
    Wong SP, Gan CY, Lim KH, Ting KN, Low YY, Kam TS
    Org. Lett., 2015 Jul 17;17(14):3628-31.
    PMID: 26183592 DOI: 10.1021/acs.orglett.5b01757
    A new monoterpene indole alkaloid characterized by an unprecedented pentacyclic cage skeleton, arboridinine (1), was isolated from a Malaysian Kopsia species. The structure and absolute configuration of the alkaloid were determined based on NMR, MS, and X-ray diffraction analysis. A possible biogenetic pathway from a pericine precursor is presented.
  9. Eosinophilic gastroenteritis: Clinical profiles and treatment outcomes, a retrospective study of 18 adult patients in a Singapore Tertiary Hospital
    Wong GW, Lim KH, Wan WK, Low SC, Kong SC
    Med J Malaysia, 2015 08;70(4):232-7.
    PMID: 26358020
    BACKGROUND: Eosinophilic gastroenteritis (EG) can mimic symptoms of common gastrointestinal (GI) disorders but responds well to appropriate treatment. Accurate diagnosis is central to effective management. Data on EG in Southeast Asia is lacking. We aim to describe the clinical profiles and treatment outcomes of adult patients with EG in a Singapore Tertiary Hospital.

    MATERIALS AND METHODS: This retrospective study involved archival search of patients with GI biopsies that showed eosinophilic infiltration from January 2004 to December 2012. Patients' clinical data from computerised hospital records and clinical notes was reviewed. Diagnostic criteria for EG included presence of GI symptoms with more than 30 eosinophils/high power field on GI biopsies. Patients with secondary causes for eosinophilia were excluded.

    RESULTS: Eighteen patients with EG were identified (mean age 52 years; male/female: 11/7). Fifteen patients (83%) had peripheral blood eosinophilia. Seven patients (39%) had atopic conditions. Most common symptoms were diarrhoea and abdominal pain. Small intestine was the most common site involved. Endoscopic finding was non-specific. Ten patients were treated with corticosteroids (nine prednisolone, one budesonide): eight patients (89%) responded clinically to prednisolone but four patients (50%) relapsed following tapering-off of prednisolone and required maintenance dose. One patient each responded to diet elimination and montelukast respectively. Half of the remaining six patients who were treated with proton-pump inhibitors, antispasmodic or antidiarrheal agents still remained symptomatic.

    CONCLUSION: Prednisolone is an effective treatment though relapses are common. Small intestine is most commonly involved. EG should be considered in the evaluation of unexplained chronic recurrent GI symptoms.

  10. Contractile function of smooth muscle retained after overnight storage
    Loong BJ, Tan JH, Lim KH, Mbaki Y, Ting KN
    Naunyn Schmiedebergs Arch Pharmacol, 2015 Oct;388(10):1061-7.
    PMID: 26051407 DOI: 10.1007/s00210-015-1140-3
    The functional responses of different overnight-stored in vitro tissues are not clearly described in any animal model. The influence of overnight storage in an animal model may vary between tissue types. We employed Sprague-Dawley rat as our animal model and investigated the functional changes of rat aorta, trachea, bronchus and bladder that were used (i) immediately after surgical removal (denoted as fresh) and (ii) after storage in aerated (95% O2, 5% CO2) Krebs-Ringer bicarbonate solution at 4 °C for 24 h (denoted as stored). The aorta ring was pre-contracted with phenylephrine, and the functional response of the tissue was investigated using isoprenaline, forskolin and carbachol. Carbachol was also used to increase the tone in trachea, bronchus rings and bladder strips. A clear reduced function of endothelium, with a minor if any effect in the smooth muscle function in rat aorta was observed after overnight storage. The contractile response of overnight-stored rat airway (trachea and bronchus) and bladder smooth muscles remained unchanged. Among all tested tissues, only bronchus showed a reduced response rate (only 40% responded) after storage. In vitro rat tissues that are stored in Krebs solution at 4 °C for 24 h can still be used to investigate smooth muscle responses, however, not endothelium-mediated responses for aorta. The influence of overnight storage on different tissues from an animal model (Sprague-Dawley rat in our study) also provides an insight in maximising the use of sacrificed animals.
  11. Fulltext Association of physical activity with blood pressure and blood glucose among Malaysian adults: a population-based study
    Teh CH, Chan YY, Lim KH, Kee CC, Lim KK, Yeo PS, et al.
    BMC Public Health, 2015;15:1205.
    PMID: 26630916 DOI: 10.1186/s12889-015-2528-1
    The health-enhancing benefits of physical activity (PA) on hypertension and diabetes have been well documented for decades. This study aimed to determine the association of PA with systolic and diastolic blood pressure as well as blood glucose in the Malaysian adult population.
  12. Alkaloid extracts of Ficus species and palm oil-derived tocotrienols synergistically inhibit proliferation of human cancer cells
    Abubakar IB, Lim KH, Loh HS
    Nat Prod Res, 2015;29(22):2137-40.
    PMID: 25515603 DOI: 10.1080/14786419.2014.991927
    Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
  13. Fulltext Inhibition of penicillin-binding protein 2a (PBP2a) in methicillin resistant Staphylococcus aureus (MRSA) by combination of ampicillin and a bioactive fraction from Duabanga grandiflora
    Santiago C, Pang EL, Lim KH, Loh HS, Ting KN
    BMC Complement Altern Med, 2015;15:178.
    PMID: 26060128 DOI: 10.1186/s12906-015-0699-z
    The inhibition of penicillin-binding protein 2a (PBP2a) is a promising solution in overcoming resistance of methicillin resistance Staphylococcus aureus (MRSA). A potential approach in achieving this is by combining natural product with currently available antibiotics to restore the activity as well as to amplify the therapeutic ability of the drugs. We studied inhibition effects of a bioactive fraction, F-10 (isolated from the leaves of Duabanga grandiflora) alone and in combination with a beta-lactam drug, ampicillin on MRSA growth and expression of PBP2a. Additionally, phytochemical analysis was conducted on F-10 to identify the classes of phytochemicals present.
  14. Fulltext Prevention of cell-surface attachment and reduction of penicillin-binding protein 2a (PBP2a) level in methicillin-resistant Staphylococcus aureus biofilms by Acalypha wilkesiana
    Santiago C, Lim KH, Loh HS, Ting KN
    BMC Complement Altern Med, 2015;15:79.
    PMID: 25880167 DOI: 10.1186/s12906-015-0615-6
    Formation of biofilm is known to enhance the virulence of methicillin-resistance Staphylococcus aureus (MRSA), which is associated with persistent infections in hospital settings. The biofilm layer essentially forms a protective barrier encapsulating the bacterial colony and thus reduces the effectiveness of chemotherapeutics. We have isolated 9EA-FC-B bioactive fraction from Acalypha wilkesiana Müll. Arg. that reverses ampicillin resistant in MRSA through inhibition of the antibiotic resistant protein, penicillin-binding protein 2a (PBP2a). In this study, we aimed to investigate the effects of 9EA-FC-B on MRSA biofilm forming capacity.
  15. The discriminative ability of waist circumference, body mass index and waist-to-hip ratio in identifying metabolic syndrome: Variations by age, sex and race
    Kee CC, Mohd Ghazali S, Lim KH, Subenthiran S, Teh CH, Lim KK, et al.
    Diabetes Metab Syndr, 2015 Apr-Jun;9(2):74-8.
    PMID: 25819369 DOI: 10.1016/j.dsx.2015.02.006
    OBJECTIVES: Many studies have suggested that there is variation in the capabilities of BMI, WC and WHR in predicting cardiometabolic risk and that it might be confounded by gender, ethnicity and age group. The objective of this study is to examine the discriminative abilities of body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) to predict two or more non-adipose components of the metabolic syndrome (high blood pressure, hypertriglyceridemia, low high density lipoprotein-cholesterol and high fasting plasma glucose) among the adult Malaysian population by gender, age group and ethnicity.
    METHODS: Data from 2572 respondents (1044 men and 1528 women) aged 25-64 years who participated in the Non Communicable Disease Surveillance 2005/2006, a population-based cross sectional study, were analysed. Participants' socio-demographic details, anthropometric indices (BMI, WC and WHR), blood pressure, fasting lipid profile and fasting glucose level were assessed. Receiver operating characteristics curves analysis was used to evaluate the ability of each anthropometric index to discriminate MetS cases from non-MetS cases based on the area under the curve.
    RESULTS: Overall, WC had better discriminative ability than WHR for women but did not perform significantly better than BMI in both sexes, whereas BMI was better than WHR in women only. Waist circumference was a better discriminator of MetS compared to WHR in Malay men and women. Waist circumference and BMI performed better than WHR in Chinese women, men aged 25-34 years and women aged 35-44 years.
    CONCLUSIONS: The discriminative ability of BMI and WC is better than WHR for predicting two or more non-adipose components of MetS. Therefore, either BMI or WC measurements are recommended in screening for metabolic syndrome in routine clinical practice in the effort to combat cardiovascular disease and type II diabetes mellitus.
    Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.
    KEYWORDS: Adult; Body mass index; Metabolic syndrome; Waist circumference; Waist–hip ratio
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey
  16. The awareness, knowledge and acceptance among KEMAS personnel towards the KOSPEN programme in Southern Zone, Malaysia. [Abstract]
    Sabtu MY, Lim KK, Ismail H, Mohd Zaki NA, Lim KH
    Med J Malaysia, 2015;70 Suppl 1:70.
    Introduction: The Ministry of Health had initiated a national programme known as “KOSPEN” to study the prevalence of Non Communicable Diseases (NCDs) and its risk factors among the population. The aim of this study is to assess the awareness, knowledge and acceptance of KOSPEN programme among
    Community Development Department (KEMAS) personnel in Southern Zone, Malaysia.
    Methods: The cross-sectional study was conducted between October and mid December 2014. The study used validated self-administered questionnaires to collect data from the 2375 KEMAS staff from the state of Johor, Malacca and Negeri Sembilan. SPSS version 20 was used for data analysis.
    Results: The results revealed that only 25.5% of respondents were aware that they were on the KOSPEN committee and 65.7% said that they knew the functions of KEMAS in KOSPEN. 90.8% were aware that their responsibilities included identifying localities for KOSPEN, identifying volunteers (85.7%) and attending KOSPEN training (75.3%). In terms of knowledge, most of them knew the objectives of KOSPEN, such as “KEMAS will add on the value of the programmes and its activities” (84.3%) and “to establish trained health volunteers in the community” (85.9%). They also knew that healthy eating habits (94.7%), active lifestyle (93.4%), body weight management (87.0%), no smoking (86.8%) and health screening (92.2%) were the components of KOSPEN. Majority of the respondents perceived that the components for intervention in the community were good. The highest accepted component was health
    screening (83.5%), follow by healthy eating habits (82.0%), active lifestyle (80.4%), no smoking habit (76.9%) and body weight management (76.1%).
    Conclusion: the awareness, knowledge and acceptance of KOSPEN programme by KEMAS personnel are good. Several measures are currently being carried out to improve and strengthen the implementation of KOSPEN programme such as funding, screening equipment and health education materials.
  17. Fulltext Lifestyle, chronic diseases and self-rated health among Malaysian adults: results from the 2011 National Health and Morbidity Survey (NHMS)
    Chan YY, Teh CH, Lim KK, Lim KH, Yeo PS, Kee CC, et al.
    BMC Public Health, 2015;15:754.
    PMID: 26246019 DOI: 10.1186/s12889-015-2080-z
    BACKGROUND: Self-rated health (SRH) has been demonstrated as a valid and appropriate predictor of incident mortality and chronic morbidity. Associations between lifestyle, chronic diseases, and SRH have been reported by various population studies but few have included data from developing countries. The aim of this study was to determine the prevalence of poor SRH in Malaysia and its association with lifestyle factors and chronic diseases among Malaysian adults.
    METHODS: This study was based on 18,184 adults aged 18 and above who participated in the 2011 National Health and Morbidity Survey (NHMS). The NHMS was a cross-sectional survey (two-stage stratified sample) designed to collect health information on a nationally representative sample of the Malaysian adult population. Data were obtained via face-to-face interviews using validated questionnaires. Two categories were used to measure SRH: "good" (very good and good) and "poor" (moderate, not good and very bad). The association of lifestyle factors and chronic diseases with poor SRH was examined using univariate and multivariate logistic regression.
    RESULTS: Approximately one-fifth of the Malaysian adult population (20.1 %) rated their health as poor (men: 18.4 % and women: 21.7 %). Prevalence increases with age from 16.2 % (aged 18-29) to 32.0 % (aged ≥60). In the multivariate logistic regression analysis, lifestyle factors associated with poor SRH included: underweight (OR = 1.29; 95 % CI: 1.05-1.57), physical inactivity (OR = 1.25; 95 % CI: 1.11-1.39), former smoker (OR = 1.38; 95 % CI: 1.12-1.70), former drinker (OR = 1.27; 95 % CI: 1.01-1.62), and current drinker (OR = 1.35; 95 % CI: 1.08-1.68). Chronic diseases associated with poor SRH included: asthma (OR = 1.66; 95 % CI: 1.36-2.03), arthritis (OR = 1.87; 95 % CI: 1.52-2.29), hypertension (OR = 1.39; 95 % CI: 1.18-1.64), hypercholesterolemia (OR = 1.43; 95 % CI: 1.18-1.74), and heart disease (OR = 1.85; 95 % CI: 1.43-2.39).
    CONCLUSIONS: This study indicates that several unhealthy lifestyle behaviours and chronic diseases are significantly associated with poor SRH among Malaysian adults. Effective public health strategies are needed to promote healthy lifestyles, and disease prevention interventions should be enhanced at the community level to improve overall health.
    Study name: National Health and Morbidity Survey (NHMS-2011)
  18. Reliability and Validity of the Fagerstrom Test for Cigarettes Dependence among Malaysian Adolescents
    Lim KH, The CH, Lim HL, Khoo YY, Lau KJ, Yy C, et al.
    Iran J Public Health, 2016 Jan;45(1):104-5.
    PMID: 27057529
  19. In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B
    Qazzaz ME, Raja VJ, Lim KH, Kam TS, Lee JB, Gershkovich P, et al.
    Cancer Lett, 2016 Jan 28;370(2):185-97.
    PMID: 26515390 DOI: 10.1016/j.canlet.2015.10.013
    Natural products play a pivotal role in medicine especially in the cancer arena. Many drugs that are currently used in cancer chemotherapy originated from or were inspired by nature. Jerantinine B (JB) is one of seven novel Aspidosperma indole alkaloids isolated from the leaf extract of Tabernaemontana corymbosa. Preliminary antiproliferative assays revealed that JB and JB acetate significantly inhibited growth and colony formation, accompanied by time- and dose-dependent apoptosis induction in human cancer cell lines. JB significantly arrested cells at the G2/M cell cycle phase, potently inhibiting tubulin polymerisation. Polo-like kinase 1 (PLK1; an early trigger for the G2/M transition) was also dose-dependently inhibited by JB (IC50 1.5 µM). Furthermore, JB provoked significant increases in reactive oxygen species (ROS). Annexin V+ cell populations, dose-dependent accumulation of cleaved-PARP and caspase 3/7 activation, and reduced Bcl-2 and Mcl-1 expression confirm apoptosis induction. Preclinical in silico biopharmaceutical assessment of JB calculated rapid absorption and bioavailability >70%. Doses of 8-16 mg/kg JB were predicted to maintain unbound plasma concentrations >GI50 values in mice during efficacy studies. These findings advocate continued development of JB as a potential chemotherapeutic agent.
  20. Arborisidine and Arbornamine, Two Monoterpenoid Indole Alkaloids with New Polycyclic Carbon-Nitrogen Skeletons Derived from a Common Pericine Precursor
    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.
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