Displaying publications 41 - 60 of 159 in total

Abstract:
Sort:
  1. Synthesis of potent urease inhibitors based on disulfide scaffold and their molecular docking studies
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Riaz M
    Bioorg Med Chem, 2015 Nov 15;23(22):7211-8.
    PMID: 26507431 DOI: 10.1016/j.bmc.2015.10.017
    Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.
  2. Synthesis, in vitro evaluation and molecular docking studies of biscoumarin thiourea as a new inhibitor of α-glucosidases
    Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F, et al.
    Bioorg Chem, 2015 Dec;63:36-44.
    PMID: 26432614 DOI: 10.1016/j.bioorg.2015.09.004
    Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5±0.39 and 104.62±0.3μM when compared with standard acarbose having IC50 value 774.5±1.94μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds can further be studied to developed lead compounds.
  3. Synthesis of novel benzohydrazone-oxadiazole hybrids as β-glucuronidase inhibitors and molecular modeling studies
    Taha M, Ismail NH, Imran S, Selvaraj M, Rahim A, Ali M, et al.
    Bioorg Med Chem, 2015 Dec 1;23(23):7394-404.
    PMID: 26526743 DOI: 10.1016/j.bmc.2015.10.037
    A series of compounds consisting of 25 novel oxadiazole-benzohydrazone hybrids (6-30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6-30 were found to be in the range of 7.14-44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain's carboxamide NH (2.1Å).
  4. Hybrid benzothiazole analogs as antiurease agent: Synthesis and molecular docking studies
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Khan KM, et al.
    Bioorg Chem, 2016 Jun;66:80-7.
    PMID: 27038849 DOI: 10.1016/j.bioorg.2016.03.010
    Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.
  5. Thiadiazole derivatives as New Class of β-glucuronidase inhibitors
    Salar U, Taha M, Ismail NH, Khan KM, Imran S, Perveen S, et al.
    Bioorg Med Chem, 2016 Apr 15;24(8):1909-18.
    PMID: 26994638 DOI: 10.1016/j.bmc.2016.03.020
    Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50=2.16±0.01-58.06±1.60μM as compare to standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques (1)H, (13)C NMR, and EIMS.
  6. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Saad SM, et al.
    Bioorg Chem, 2016 Jun;66:117-23.
    PMID: 27149363 DOI: 10.1016/j.bioorg.2016.04.006
    Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction.
  7. Synthesis and biological evaluation of novel N-arylidenequinoline-3-carbohydrazides as potent β-glucuronidase inhibitors
    Taha M, Sultan S, Nuzar HA, Rahim F, Imran S, Ismail NH, et al.
    Bioorg Med Chem, 2016 08 15;24(16):3696-704.
    PMID: 27312423 DOI: 10.1016/j.bmc.2016.06.008
    Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
  8. Synthesis, biological evaluation, and docking studies of novel thiourea derivatives of bisindolylmethane as carbonic anhydrase II inhibitor
    Imran S, Taha M, Ismail NH, Fayyaz S, Khan KM, Choudhary MI
    Bioorg Chem, 2015 Oct;62:83-93.
    PMID: 26275866 DOI: 10.1016/j.bioorg.2015.08.001
    This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place.
  9. Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors
    Taha M, Ismail NH, Imran S, Rokei MQB, Saad SM, Khan KM
    Bioorg Med Chem, 2015 Aug 01;23(15):4155-4162.
    PMID: 26183542 DOI: 10.1016/j.bmc.2015.06.060
    Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.
  10. Pesticides Exposure and Cardiovascular Hemodynamic Parameters Among Male Workers Involved in Mosquito Control in East Coast of Malaysia
    Samsuddin N, Rampal KG, Ismail NH, Abdullah NZ, Nasreen HE
    Am J Hypertens, 2016 Feb;29(2):226-33.
    PMID: 26112865 DOI: 10.1093/ajh/hpv093
    Research findings have linked exposure to pesticides to an increased risk of cardiovascular (CVS) diseases. Therefore, this study aimed to assess the impact of chronic mix-pesticides exposure on CVS hemodynamic parameters.
  11. Non-occupational exposure of Malay women in Kuala Lumpur, Malaysia, to cadmium and lead
    Moon CS, Zhang ZW, Watanabe T, Shimbo S, Ismail NH, Hashim JH, et al.
    Biomarkers, 1996;1(2):81-5.
    PMID: 23888917 DOI: 10.3109/13547509609088674
    Abstract Peripheral blood and 24-h total food duplicate samples were obtained from 49 adult Malay women in Kuala Lumpur, Malaysia, in July, 1995. Samples of boiled and uncooked (raw) rice were also collected from the subjects. The blood samples, homogenates of each food duplicates and rice samples (both cooked and raw) were digested by heating in the presence of mineral acids, and the digests were subjected to analysis for cadmium (Cd) and lead (Pb) with a system composed of a fully automated liquid sampler, a graphiie furnace atomic absorption spectrometer and a data processor. The geometric mean metal concentrations in blood were 0.71 ng Cd per ml and 45.6 ng Pb per ml, and the dietary metal intakes were 7.31 μg Cd per day and 10.1 μg Pb per day. The metal intake via rice accounted for 53% and 13% of total dietary intake of cadmium and lead, respectively. When the absorption from the air and foods was compared, the cadmium burden came almost exclusively from foods, whereas the lead burden came both from air (44%) and foods (56%).
  12. Nutritional evaluation of working Malay women in Kuala Lumpur as studied by total food duplicate method
    Shimbo S, Moon CS, Zhang ZW, Watanabe T, Ismail NH, Ali RM, et al.
    Tohoku J. Exp. Med., 1996 Oct;180(2):99-114.
    PMID: 9111760
    Nutrient intake was surveyed by the total food duplicate method in 49 adult ethnically Malay women (at the ages of 18 to 47 years and mostly at 30-39 years) working in Kuala Lumpur, Malaysia. Simultaneously, hematological examinations, serum biochemistry, anthropometry and clinical examination were conducted. Nutrient intakes were estimated in reference to the weight of each food item and the standard food composition tables. Lunch was the most substantial meal of the day with rice as a staple food. Compared with the Recommended Dietary Allowance (RDA) values, daily intakes of energy (1,917 kcal as an arithmetic mean), protein (62.2 g), vitamin B1 (0.83 mg) and vitamin B2 (1.18 mg) were sufficient, but intakes of minerals [i.e., calcium (347.8 mg) and iron (12.5 mg)] and some vitamins [i.e., vitamin A (equivalent to 627 micrograms retinol) and niacin (7.84 mg)] were less than RDA. When evaluated on an individual basis, the prevalence of those who took less than 80% RDA was highest for iron (92%), followed by niacin (80%), calcium (57%) and vitamin A (57%). The presence of 7 hypohemoglobinemia cases may be related to the insufficient iron intake. Overweight cases (14 women) were also detected, the prevalence of which increased at advanced ages. Lipid intake was rather high (28% of total food on energy basis), for which the major source was plants with limited contribution from fish/shellfish.
  13. Dislodgement resistance and adhesive pattern of different endodontic sealers to dentine wall after artificial ageing: an in-vitro study
    Lin GSS, Ghani NRNA, Noorani TY, Ismail NH, Mamat N
    Odontology, 2021 Jan;109(1):149-156.
    PMID: 32623538 DOI: 10.1007/s10266-020-00535-7
    To compare the dislodgement resistance and the adhesive pattern of four different endodontic sealers to root dentine walls. Ninety lower premolars were assigned to five groups (n = 18), Group 1: no sealer (control); Group 2: EndoRez (ERZ); Group 3: Sealapex (SPX); Group 4: EndoSeal MTA (ESA) and Group 5: BioRoot RCS (BRS). They were instrumented up to size 30 taper 0.06 and obturated using single cone technique with matched-taper gutta-percha cones and one of the mentioned sealers. Six teeth from each group were then randomly subjected to 100, 1000 and 10,000 thermocycles, respectively. 1 mm slice of mid root region, measuring 6 mm from the apical foramen was prepared and subjected to push-out test under a Universal Testing Machine. Adhesive patterns of sealers were assessed using a stereomicroscope at 20 × magnification and classified using a new system. Statistical analyses were performed using two-way ANOVA, complemented by Tukey HSD and Chi-square tests. ESA and BRS showed significantly higher (p  0.05) at 100, 1000 and 10,000 thermocycles, respectively. Both ESA and BRS exhibited a significant higher rate (p 
  14. Fulltext Adverse Effects of Wi-Fi Radiation on Male Reproductive System: A Systematic Review
    Jaffar FHF, Osman K, Ismail NH, Chin KY, Ibrahim SF
    Tohoku J. Exp. Med., 2019 07;248(3):169-179.
    PMID: 31353326 DOI: 10.1620/tjem.248.169
    Extensive use of Wi-Fi has contributed to radiofrequency electromagnetic radiation (RF-EMR) pollution in environment. Various studies have been conducted to evaluate the effect of RF-EMR emitted by Wi-Fi transmitter on male reproduction health. However, there are conflicting findings between studies. Thus, this review aims to elucidate the possible effects of 2.45 GHz Wi-Fi exposure on both animal and human male reproductive system. A computerized database search performed through MEDLINE via Ovid and PUBMED with the following set of keywords: 'Wi-Fi or WiFi or wireless fidelity or Wi-Fi router or WiFi router or electromagnetic or radiofrequency radiation' AND 'sperm or spermatozoa or spermatogenesis or semen or seminal plasma or testes or testis or testosterone or male reproduction' had returned 526 articles. Only 17 studies conformed to pre-set inclusion criterion. Additional records identified through Google Scholar and reviewed article further revealed six eligible articles. A total of 23 articles were used for data extraction, including 15 studies on rats, three studies on mice, and five studies on human health. Sperm count, motility and DNA integrity were the most affected parameters when exposed to RF-EMR emitted by Wi-Fi transmitter. Unfortunately, sperm viability and morphology were inconclusive. Structural and/or physiological analyses of the testes showed degenerative changes, reduced testosterone level, increased apoptotic cells, and DNA damage. These effects were mainly due to the elevation of testicular temperature and oxidative stress activity. In conclusion, exposure towards 2.45 GHz RF-EMR emitted by Wi-Fi transmitter is hazardous on the male reproductive system.
  15. Fulltext Augmentation of the Female Reproductive System Using Honey: A Mini Systematic Review
    Ismail NH, Ibrahim SF, Jaffar FHF, Mokhtar MH, Chin KY, Osman K
    Molecules, 2021 Jan 27;26(3).
    PMID: 33513715 DOI: 10.3390/molecules26030649
    Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in vivo on the FRS remain unclear. This review aims to investigate the current literature on the effects of HS on the FRS, particularly on the sex hormone profile and reproductive organs (uterus and vagina). A systematic literature search using Scopus, MEDLINE via Ovid and Cochrane Library databases was conducted. Records were screened and identified for preclinical and clinical studies addressing the effects of HS on the FRS. Data on populations, interventions, outcomes and methodological quality were extracted. Studies were synthesised using tables and written summaries. Of the 198 identified records, six fulfilled the inclusion criteria. All six records were used for data extraction: two experimental studies using rats as the model organism and four human clinical studies of honey on female reproductive health. HS elevated the progesterone levels, restrained body weight increase, prevented uterine and vaginal atrophies in ovariectomised rats, attenuated symptoms of candidiasis and improved oxidative status in patients. Current evidence shows that short-term HS following surgical or physiological menopause exerts an oestrogenic, antioxidant and anti-inflammatory effect on the FRS. However, insufficient long-term studies preclude any definitive conclusions.
  16. Healthcare practitioner behaviours that influence unsafe use of hospital information systems
    Salahuddin L, Ismail Z, Hashim UR, Ismail NH, Raja Ikram RR, Abdul Rahim F, et al.
    Health Informatics J, 2020 Mar;26(1):420-434.
    PMID: 30843460 DOI: 10.1177/1460458219833090
    This study aims to investigate healthcare practitioner behaviour in adopting Health Information Systems which could affect patients' safety and quality of health. A qualitative study was conducted based on a semi-structured interview protocol on 31 medical doctors in three Malaysian government hospitals implementing the Total Hospital Information Systems. The period of study was between March and May 2015. A thematic qualitative analysis was performed on the resultant data to categorize them into relevant themes. Four themes emerged as healthcare practitioners' behaviours that influence the unsafe use of Hospital Information Systems. The themes include (1) carelessness, (2) workarounds, (3) noncompliance to procedure, and (4) copy and paste habit. By addressing these behaviours, the hospital management could further improve patient safety and the quality of patient care.
  17. Blood pressure lowering effect of Ficus deltoidea var kunstleri in spontaneously hypertensive rats: possible involvement of renin-angiotensin-aldosterone system, endothelial function and anti-oxidant system
    Azis NA, Agarwal R, Ismail NM, Ismail NH, Kamal MSA, Radjeni Z, et al.
    Mol Biol Rep, 2019 Jun;46(3):2841-2849.
    PMID: 30977084 DOI: 10.1007/s11033-019-04730-w
    This study investigated the effects of a standardised ethanol and water extract of Ficus deltoidea var. Kunstleri (FDK) on blood pressure, renin-angiotensin-aldosterone system (RAAS), endothelial function and antioxidant system in spontaneously hypertensive rats (SHR). Seven groups of male SHR were administered orally in volumes of 0.5 mL of either FDK at doses of 500, 800, 1000 and 1300 mg kg- 1, or captopril at 50 mg kg- 1 or losartan at 10 mg kg- 1 body weight once daily for 4 weeks or 0.5 mL distilled water. Body weight, systolic blood pressures (SBP) and heart rate (HR) were measured every week. 24-hour urine samples were collected at weeks 0 and 4 for electrolyte analysis. At week 4, sera from rats in the control and 1000 mg kg- 1 of FDK treated groups were analyzed for electrolytes and components of RAAS, endothelial function and anti-oxidant capacity. SBP at week 4 was significantly lower in all treatment groups, including captopril and losartan, when compared to that of the controls. Compared to the controls, ACE activity and concentrations of angiotensin I, angiotensin II and aldosterone were lower whereas concentrations of angiotensinogen and angiotensin converting enzyme 2 were higher in FDK treated rats. Concentration of eNOS and total anti-oxidant capacity were higher in FDK treated rats. Urine calcium excretion was higher in FDK treated rats. In conclusion, it appears that ethanol and water extract of FDK decreases blood pressure in SHR, which might involve mechanisms that include RAAS, anti-oxidant and endothelial system.
  18. Fulltext Polymerization Shrinkage and Degree of Conversion of New Zirconia-Reinforced Rice Husk Nanohybrid Composite
    Lin GSS, Abdul Ghani NRN, Ismail NH, Singbal KP, Yusuff NMM
    Eur J Dent, 2020 Jul;14(3):448-455.
    PMID: 32599624 DOI: 10.1055/s-0040-1713951
    OBJECTIVES:  This study aimed to compare the polymerization shrinkage and degree of conversion of new zirconia-reinforced rice husk nanohybrid composite with commercialized microhybrid and nanofilled composites.

    MATERIALS AND METHODS:  Overall, 180 samples were used for polymerization shrinkage (buoyancy and optical methods) and degree of conversion tests in which they were divided into Group 1, nanofilled composite (Filtek-Z350- XT; 3M ESPE, St Paul, MN 55144-1000, USA), Group 2, microhybrid composite (Zmack-Comp), and Group 3, nanohybrid composite (Zr-Hybrid). Polymerization shrinkage test was performed using buoyancy and optical methods. For buoyancy method, samples were weighed in air and water to calculate the shrinkage value, whereas, for optical method, images of nonpolymerized samples were captured under a digital microscope and recaptured again after light-cured to calculate the percentage of shrinkage. Degree of conversion was tested using Fourier-transform infrared spectroscopy spectrometer.

    STATISTICAL ANALYSIS:  Data were analyzed using one-way analysis of variance complemented by post hoc Dunnett's T3 test for polymerization shrinkage and Tukey's honestly significant difference test for degree of conversion. Level of significance was set at p < 0.05.

    RESULTS:  Group 3 demonstrated similar polymerization shrinkage with Group 1, but lower shrinkage (p < 0.05) than Group 2 based on buoyancy method. However, optical method (p < 0.05) showed that Group 3 had the lowest shrinkage, followed by Group 1 and lastly Group 2. Besides, Group 3 showed a significantly higher degree of conversion (p < 0.05) than Group 1 and comparable conversion value with Group 2.

    CONCLUSIONS:  Zirconia-reinforced rice husk nanohybrid composite showed excellent shrinkage and conversion values, hence can be considered as an alternative to commercially available composite resins.

  19. Synthesis of 2-methoxybenzoylhydrazone and evaluation of their antileishmanial activity
    Taha M, Baharudin MS, Ismail NH, Khan KM, Jaafar FM, Samreen, et al.
    Bioorg Med Chem Lett, 2013 Jun 1;23(11):3463-6.
    PMID: 23608761 DOI: 10.1016/j.bmcl.2013.03.051
    Compounds 1-25 showed varying degree of antileishmanial activities with IC50 values ranging between 1.95 and 88.56 μM. Compounds 2, 10, and 11 (IC50=3.29±0.07 μM, 1.95±0.04 μM, and 2.49±0.03 μM, respectively) were found to be more active than standard pentamidine (IC50=5.09±0.04 μM). Compounds 7 (IC50=7.64±0.1 μM), 8 (IC50=13.17±0.46 μM), 18 (IC50=13.15±0.02 μM), and 24 (IC50=15.65±0.41 μM) exhibited good activities. Compounds 1, 3, 4, 5, 9, 12, 15, 18, and 19 were found to be moderately active. Compounds 13, 14, 16, 17, 20-25 showed weak activities with IC50 values ranging between 57 and 88 μM.
  20. Telomerase reverse transcriptase downregulation by RNA interference modulates endoplasmic reticulum stress and mitochondrial energy production
    Mohd Zain MZ, Ismail NH, Ahmad N, Sulong S, Karsani SA, Abdul Majid N
    Mol Biol Rep, 2020 Oct;47(10):7735-7743.
    PMID: 32959195 DOI: 10.1007/s11033-020-05848-y
    Telomerase is a cancer promoting ribonucleoprotein complex and is a potential therapeutic target for cancer. In this study, the effects of telomerase downregulation on the whole cell proteome were investigated. Understanding how the effect of downregulation on the whole proteome profile will generate a greater understanding of the possible roles played by telomerase in cancer. Downregulation was achieved by RNA interference (RNAi), targeting the telomerase reverse transcriptase (TERT) subunits of telomerase. Transfection of TERT siRNA downregulates TERT gene expression and induced downregulation of telomerase activity. Investigation of the effect of silencing TERT in telomerase was further validated through proteomic analysis by performing 2-dimension electrophoresis (2DE) coupled with MALDI-TOF/TOF. 12 protein spots in HeLa cells were reported to be significantly differentially expressed with 11 of them were upregulated and 1 downregulated. Through STRING analysis, differentially expressed proteins demonstrated strong associations with endoplasmic reticulum stress marker and mitochondrial energy production marker. In conclusions, the result exhibited novel integrated proteomic response involving endoplasmic reticulum stress and mitochondrial energy production in response to the TERT downregulation in cervical cancer cells.
Related Terms
Filters
Contact Us

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

External Links