MyMedR

Displaying publications 61 - 80 of 127 in total

Abstract:

Sort:

Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study

Ulaganathan V, Kandiah M, Zalilah MS, Faizal JA, Fijeraid H, Normayah K, et al.

Asian Pac J Cancer Prev, 2012;13(8):3873-7.
PMID: 23098486

OBJECTIVE: Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two.
METHODS: Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280).
RESULTS: MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed.
CONCLUSION: This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.
Fulltext Validation of quantitative structure-activity relationship (QSAR) model for photosensitizer activity prediction

Frimayanti N, Yam ML, Lee HB, Othman R, Zain SM, Rahman NA

Int J Mol Sci, 2011;12(12):8626-44.
PMID: 22272096 DOI: 10.3390/ijms12128626

Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r(2) value, r(2) (CV) value and r(2) prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC(50) values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r(2) prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.
New bioactive glass-ceramic: synthesis and application in PMMA bone cement composites

Abd Samad H, Jaafar M, Othman R, Kawashita M, Abdul Razak NH

Biomed Mater Eng, 2011;21(4):247-58.
PMID: 22182792 DOI: 10.3233/BME-2011-0673

In present study, a new composition of glass-ceramic was synthesized based on the Na2O-CaO-SiO2-P2O5 glass system. Heat treatment of glass powder was carried out in 2 stages: 600 °C as the nucleation temperature and different temperature on crystallization at 850, 950 and 1000 °C. The glass-ceramic heat-treated at 950 °C was selected as bioactive filler in commercial PMMA bone cement; (PALACOS® LV) due to its ability to form 2 high crystallization phases in comparison with 850 and 1000 °C. The results of this newly glass-ceramic filled PMMA bone cement at 0-16 wt% of filler loading were compared with those of hydroxyapatite (HA). The effect of different filler loading on the setting properties was evaluated. The peak temperature during the polymerization of bone cement decreased when the liquid to powder (L/P) ratio was reduced. The setting time, however, did not show any trend when filler loading was increased. In contrast, dough time was observed to decrease with increased filler loading. Apatite morphology was observed on the surface of the glass-ceramic and selected cement after bioactivity test.
Fate of napropamide herbicide in selected Malaysian soils

Sadegh-Zadeh F, Wahid SA, Seh-Bardan BJ, Othman R, Omar D

J Environ Sci Health B, 2012;47(2):144-51.
PMID: 22251214 DOI: 10.1080/03601234.2012.624481

This study was carried out to determine the sorption-desorption, degradation and leaching of napropamide in selected Malaysian soils. The sorption capacities of the selected Malaysian soils for napropamide were the following in descending order: Linau > Teringkap > Gunung Berinchang > Jambu > Rudua > Baging soil. The results indicate that napropamide degradation decreased with increasing soil sorption capacity. Napropamide was leached out earlier in the Baging soil than the other soils. Overall, the application of napropamide in the selected Malaysian soils would not pose a threat to the environment except in soil with low organic matter and clay content and high hydraulic conductivity, such as the Baging soil.
Relative salinity tolerance of warm season turfgrass species

Uddin KM, Juraimi AS, Ismail MR, Othman R, Rahim AA

J Environ Biol, 2011 May;32(3):309-12.
PMID: 22167942

Fresh water, coupled with soil salinization in many areas has resulted in an increased need forscreening of salt tolerant turf grasses. Relative salinity tolerance of eightwarm season turfgrass species were examined in this study in sand culture. Grasses were grown in a glasshouse, irrigated with either distilled water or saline sea water adjusted to 24, 48 or 72 dSm-1. Salt tolerances of the grasses were assessed on the basis of their shoot and root growth, leaf firing and turf quality. Regression analysis indicated that Zoysiajaponica (Japanese lawn grass) (JG), Stenotaphrum secundatum (St. Augustine) (SA), Cynodon dactylon (satiri) (BS), Zoysia teneuifolia (Korean grass) (KG), Digitaria didactyla (Serangoon grass) (SG), Cynodon dactylon (Tifdwarf) (TD), Paspalum notatum (Bahia grass) (BG) and Axonopus compressus(Pearl blue) (PB) suffered a 50% shoot growth reduction at 36.0, 31.8, 30.9, 28.4, 26.4, 25.7, 20.0 and 18.6 dSm1 of salinity, respectively and a root growth reduction at44.9, 43.7, 33.4, 31.0, 29.5 27.5, 21.5 and 21.4 dSm- of salinity, respectively. Leaf firing and turf quality of the selected species, as a whole, were also found to be affected harmoniously with the change in root and shoot growth. On the basis of the experimental results the selected species were ranked for salinity tolerance as JG>SA>BS>KG>SG >TD>BG>PB.
Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites

Othman R, Kiat TS, Khalid N, Yusof R, Newhouse EI, Newhouse JS, et al.

J Chem Inf Model, 2008 Aug;48(8):1582-91.
PMID: 18656912 DOI: 10.1021/ci700388k

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.
Rational discovery of dengue type 2 non-competitive inhibitors

Heh CH, Othman R, Buckle MJ, Sharifuddin Y, Yusof R, Rahman NA

Chem Biol Drug Des, 2013 Jul;82(1):1-11.
PMID: 23421589 DOI: 10.1111/cbdd.12122

Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.
Fulltext Dataset for assessing the efficiency factors in Malaysian ports: Dry bulk terminal

Rozar NM, Razik MA, Sidik MH, Kamarudin S, Ismail MR, Azid A, et al.

Data Brief, 2020 Aug;31:105858.
PMID: 32637478 DOI: 10.1016/j.dib.2020.105858

This research paper provides for the identification of dry bulk terminal efficiencies on the basis of 10 key performance factors in Malaysian ports. Data were collected from 18 dry bulk ports in Malaysia in 2017 through an online questionnaire and distributed via e-mail. The dispersion of the respondents corresponds approximately to the structure of the Malaysian maritime terminal in dry bulk. The data provides port management perceptions towards 10 variables that have been surveyed. Each perception assessed the level of efficiency factors based on a percentage rate of 100%. Efficiency factors in dry bulk terminals have been identified with varying characteristics based on a descriptive analysis table. The dataset presented consists of a brief analysis of all 10 variables involved, including the minimum, maximum, mean, interquartile median and standard deviation. In addition to the descriptive analysis, the normality test and histogram were also performed. Data can be used to measure ports-efficiency factors in another research.
Fulltext Transcriptome data of the carrageenophyte Eucheuma denticulatum

Othman R, Abd Rasib AA, Ilias MA, Murthy S, Ismail N, Mohd Hanafi N

Data Brief, 2019 Jun;24:103824.
PMID: 30984808 DOI: 10.1016/j.dib.2019.103824

Eucheuma denticulatum or commonly known as "Spinosum", is an economically important red alga that naturally grows on coral reefs with moderately strong currents in tropical and sub-tropical areas. This species is the primary source of iota-carrageenan which has high demands in the food, pharmaceutical and manufacturing industries, and as such it has been widely cultivated. The increasing global demand for carrageenan has led to extensive commercial cultivation of carrageenophytes mainly in the tropics. The carrageenophyte seaweeds including E. denticulatum are indigenous to Sabah, Malaysia. To enrich the information on the genes involved in carrageenan biosynthesis, RNA sequencing has been performed and transcriptomic dataset has been generated using Illumina HiSeq™ 2000 sequencer. The raw data and transcriptomic data have been deposited in NCBI database with the accession number PRJNA477734. These data will provide valuable resources for functional genomics annotation and investigation of mechanisms underlying the regulations of genes in this algal species.
Monoterpene alcohol metabolism: identification, purification, and characterization of two geraniol dehydrogenase isoenzymes from Polygonum minus leaves

Hassan M, Maarof ND, Ali ZM, Noor NM, Othman R, Mori N

Biosci Biotechnol Biochem, 2012;76(8):1463-70.
PMID: 22878188

NADP(+)-dependent geraniol dehydrogenase (EC 1.1.1.183) is an enzyme that catalyzes the oxidation of geraniol to geranial. Stable, highly active cell-free extract was obtained from Polygonum minus leaves using polyvinylpolypyrrolidone, Amberlite XAD-4, glycerol, 2-mercaptoethanol, thiourea, and phenylmethylsulfonylfluoride in tricine-NaOH buffer (pH 7.5). The enzyme preparation was separated into two activity peaks, geraniol-DH I and II, by DEAE-Toyopearl 650M column chromatography at pH 7.5. Both isoenzymes were purified to homogeneity in three chromatographic steps. The geraniol-DH isoenzymes were similar in molecular mass, optimal temperature, and pH, but the isoelectric point, substrate specificity, and kinetic parameters were different. The K(m) values for geraniol of geraniol-DH I and II appeared to be 0.4 mM and 0.185 mM respectively. P. minus geraniol-DHs are unusual among geraniol-DHs in view of their thermal stability and optimal temperatures, and also their high specificity for allylic alcohols and NADP(+).
Rapid detection of α-thalassaemia variants using droplet digital PCR

Lee TY, Lai MI, Ramachandran V, Tan JA, Teh LK, Othman R, et al.

Int J Lab Hematol, 2016 Aug;38(4):435-43.
PMID: 27349818 DOI: 10.1111/ijlh.12520

INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately.
METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR).
RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously.
CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.
Fulltext -Chemical profiling and biological activity of Peperomia blanda (Jacq.) Kunth

Al-Madhagi WM, Mohd Hashim N, Awad Ali NA, Alhadi AA, Abdul Halim SN, Othman R

PeerJ, 2018;6:e4839.
PMID: 29892499 DOI: 10.7717/peerj.4839

Background: Peperomia belongs to the family of Piperaceae. It has different uses in folk medicine and contains rare compounds that have led to increased interest in this genus. Peperomia blanda (Jacq.) Kunth is used as an injury disinfectant by Yemeni people. In addition, the majority of Yemen's population still depend on the traditional remedy for serious diseases such as cancer, inflammation and infection. Currently, there is a deficiency of scientific evidence with regards to the medicinal plants from Yemen. Therefore, this study was performed to assess the chemical profile and in vitro antioxidant and cytotoxic activities of P. blanda.
Methods: Chemical profiling of P. blanda was carried out using gas chromatography mass spectrometry (GCMS) followed by isolation of bioactive compounds by column chromatography. DPPH• and FRAP assays were used to evaluate antioxidant activity and the MTT assay was performed to estimate the cytotoxicity activity against three cancer cell lines, namely MCF-7, HL-60 and WEHI-3, and three normal cell lines, MCF10A, WRL-68 and HDFa.
Results: X-ray crystallographic data for peperomin A is reported for the first time here and N,N'-diphenethyloxamide was isolated for the first time from Peperomia blanda. Methanol and dichloromethane extracts showed high radical scavenging activity with an IC50 of 36.81 ± 0.09 µg/mL, followed by the dichloromethane extract at 61.78 ± 0.02 µg/mL, whereas the weak ferric reducing activity of P. blanda extracts ranging from 162.2 ± 0.80 to 381.5 ± 1.31 µg/mL were recorded. In addition, petroleum ether crude extract exhibited the highest cytotoxic activity against all the tested cancer cell lines with IC50 values of 9.54 ± 0.30, 4.30 ± 0.90 and 5.39 ± 0.34 µg/mL, respectively. Peperomin A and the isolated mixture of phytosterol (stigmasterol and β-sitosterol) exhibited cytotoxic activity against MCF-7 and WE-HI cell lines with an IC50 of (5.58 ± 0.47, 4.62 ± 0.03 µg/mL) and (8.94 ± 0.05, 9.84 ± 0.61 µg/mL), respectively, compared to a standard drug, taxol, that has IC50 values of 3.56 ± 0.34 and 1.90 ± 0.9 µg/mL, respectively.
Conclusion: The activities of P. blanda extracts and isolated compounds recorded in this study underlines the potential that makes this plant a valuable source for further study on anticancer and antioxidant activities.
Fulltext Carotenoids of Capsicum Fruits: Pigment Profile and Health-Promoting Functional Attributes

Mohd Hassan N, Yusof NA, Yahaya AF, Mohd Rozali NN, Othman R

Antioxidants (Basel), 2019 Oct 09;8(10).
PMID: 31600964 DOI: 10.3390/antiox8100469

Pepper of the Capsicum species is a common ingredient in various food preparations by different cultures worldwide. The Capsicum is recognised by its five main domesticated species, namely Capsicum annuum, C. baccatum, C. chinense, C. frutescens and C. pubescens. The genetic diversity in Capsicum offers fruits in wide ranges of morphology and carotenoid profile. Carotenoids enhance the value of pepper from a nutritional standpoint, despite being commonly prized for the pharmacologically active pungent capsaicinoids. Carotenoids of pepper comprise mainly of the unique, powerful and highly stable capsanthin and capsoroubin, together with β-carotene, β-cryptoxanthin, lutein, zeaxanthin, antheraxanthin and violaxanthin. These carotenoids are present at diverse profile and varying levels, biosynthetically connected to the fruit maturity stages. This review describes the health-promoting functional attributes of the carotenoids that are mainly associated with their excellent role as lipophilic antioxidants. Capsicum as a great source of carotenoids is discussed in the aspects of main domesticated species, biosynthesis, pigment profile, antioxidant activity and safety. Findings from a number of in vitro, in vivo and clinical studies provided appreciable evidence on the protective effects of pepper's carotenoids against degenerative diseases. Hence, pepper with its functional carotenoids might be recommended in health-promoting and disease preventing strategies.
Bioluminescent method for the rapid screening of toxic heayy metals in environmental samples using Photobacterium leiognathi strain AK-MIE

Kassim A, Halmi MIE, Gani SSA, Zaidan UH, Othman R, Mahmud K, et al.

Ecotoxicol Environ Saf, 2020 Jun 15;196:110527.
PMID: 32278138 DOI: 10.1016/j.ecoenv.2020.110527

Assessment of eco-toxicant using bioluminescent bacterial assay is a widely used and globally accepted method. In this work, a new luminescent bacterium was isolated from squid (Loligo duvauceli) and identified as Photobacterium leiognathi strain AK-MIE using 16S rRNA, phylogeny analysis. The predicted optimum conditions by RSM were 2.76% (w/v) NaCl, 2.28% (w/v) peptone, 0.34% (w/v) yeast extract, and pH 6.83 with 541,211.80 RLU of luminescent production whereas the predicted optimum conditions by ANN were 2.21% (w/v) NaCl, 2.27% (w/v) peptone, 0.39% (w/v) yeast extract, and pH 6.94 which produced 541,986.20 RLU. The validation analysis of both RSM and ANN show 0.60% and 0.69% deviation from the predicted results indicating that both models provided good quality predictions with ANN showing a superior data fitting capability for non-linear regression analysis. Toxicity tests show strain AK-MIE was sensitive to mercury (concentration causing 50% inhibition or IC50 of 0.00978 mgL-1), followed by cadmium (IC50 of 0.5288 mgL-1), copper IC50 of (0.8117 mgL-1), silver (IC50 of 1.109 mgL-1), and lead (IC50 of 10.71 mgL-1) which are more sensitive than previously isolated luminescent bacteria, suggesting that strain AK-MIE has the potential to be used in toxicity assessment of heavy metals in the environment. Based on the field trial results, several sediment samples from industrial areas in Bangi, Selangor managed to inhibit the bioluminescence of strain AK-MIE. Validation method carried out using ICP-MS proved the presence of several toxic heavy metal elements.
Site-directed mutagenesis of β sesquiphellandrene synthase enhances enzyme promiscuity

Ker DS, Chan KG, Othman R, Hassan M, Ng CL

Phytochemistry, 2020 May;173:112286.
PMID: 32059132 DOI: 10.1016/j.phytochem.2020.112286

The chemical formation of terpenes in nature is carried out by terpene synthases as the main biocatalysts to guide the carbocation intermediate to form structurally diverse compounds including acyclic, mono- and multiple cyclic products. Despite intensive study of the enzyme active site, the mechanism of specific terpene biosynthesis remains unclear. Here we demonstrate that a single mutation of the amino acid L454G or L454A in the active site of Persicaria minor β-sesquiphellandrene synthase leads to a more promiscuous enzyme that is capable of producing additional hydroxylated sesquiterpenes such as sesquicineole, sesquisabinene hydrate and α-bisabolol. Furthermore, the same L454 residue mutation (L454G or L454A) in the active site also improves the protein homogeneity compared to the wild type protein. Taken together, our results demonstrate that residue Leucine 454 in the active site of β-sesquiphellandrene synthase is important for sesquiterpene product diversity as well as the protein homogeneity in solution.
The effect of methyltestosterone (MT) on sex differentiation and growth in juvenile yellow perch (Perca flavescens)

Othman R, Ron XJ, Yao H, O'Bryant P, Rapp D, Pei JC, et al.

Fish Physiol Biochem, 2022 Feb;48(1):161-171.
PMID: 35039993 DOI: 10.1007/s10695-021-01038-0

A study was conducted to evaluate the gonad differentiation of juvenile yellow perch (YP, Perca flavencens) and determine the latest labile period related to hormone treatment. Juvenile fish were subjected to two dietary concentrations of methyltestosterone (MT; 20 and 50 mg/kg feed) for 60 days in three (3) age groups of 38-, 46-, and 67-days post-hatching (dph), where control group were fed with standard commercial feed. Following a 10-month on-growing period, sex phenotypes were determined by gross and histological gonad morphology. Results showed the juvenile YP responded to the exogenous hormone when it was applied at 38 dph for both 20 and 50 mg/kg feed resulting in 100% males. At 46 dph, only 50 mg/kg feed resulted in 100% males. Both MT-treated at 38 and 46 dph significantly differed (P
Fulltext Biomedical PEVA Nanocomposite with Dual Clay Nanofiller: Cytotoxicity, Mechanical Properties, and Biostability

Mohammed Fitri TF, Osman AF, Alosime EM, Othman R, Hashim F, Abdullah MAA

Polymers (Basel), 2021 Dec 12;13(24).
PMID: 34960896 DOI: 10.3390/polym13244345

Poly(ethylene-vinyl acetate) (PEVA) nanocomposite incorporating dual clay nanofiller (DCN) of surface modified montmorillonite (S-MMT) and bentonite (Bent) was studied for biomedical applications. In order to overcome agglomeration of the DCN, the S-MMT and Bent were subjected to a physical treatment prior to being mixed with the copolymer to form nanocomposite material. The S-MMT and Bent were physically treated to become S-MMT(P) and Bent(pH-s), respectively, that could be more readily dispersed in the copolymer matrix due to increments in their basal spacing and loosening of their tactoid structure. The biocompatibility of both nanofillers was assessed through a fibroblast cell cytotoxicity assay. The mechanical properties of the neat PEVA, PEVA nanocomposites, and PEVA-DCN nanocomposites were evaluated using a tensile test for determining the best S-MMT(P):Bent(pH-s) ratio. The results were supported by morphological studies by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Biostability evaluation of the samples was conducted by comparing the ambient tensile test data with the in vitro tensile test data (after being immersed in simulated body fluid at 37 °C for 3 months). The results were supported by surface degradation analysis. Our results indicate that the cytotoxicity level of both nanofillers reduced upon the physical treatment process, making them safe to be used in low concentration as dual nanofillers in the PEVA-DCN nanocomposite. The results of tensile testing, SEM, and TEM proved that the ratio of 4:1 (S-MMT(P):Bent(pH-s)) provides a greater enhancement in the mechanical properties of the PEVA matrix. The biostability assessment indicated that the PEVA-DCN nanocomposite can achieve much better retention in tensile strength after being subjected to the simulated physiological fluid for 3 months with less surface degradation effect. These findings signify the potential of the S-MMT(P)/Bent(pH-s) as a reinforcing DCN, with simultaneous function as biostabilizing agent to the PEVA copolymer for implant application.
Fulltext Synthesis, Biological Evaluation and Molecular Modelling of 2'-Hydroxychalcones as Acetylcholinesterase Inhibitors

Sukumaran SD, Chee CF, Viswanathan G, Buckle MJ, Othman R, Abd Rahman N, et al.

Molecules, 2016 Jul 22;21(7).
PMID: 27455222 DOI: 10.3390/molecules21070955

A series of 2'-hydroxy- and 2'-hydroxy-4',6'-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40-85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.
Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells

Nordin N, Majid NA, Othman R, Omer FAA, Nasharuddin MNA, Hashim NM

Apoptosis, 2018 02;23(2):152-169.
PMID: 29430581 DOI: 10.1007/s10495-018-1447-x

Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC50 of 0.62 µM. The existence of apoptotic bodies, cell membrane blebbing and chromatin condensation indicated the hallmark of apoptosis. Increase of Annexin V-FITC bound to phosphatidylserine confirmed the apoptosis induction in the cells. The apoptosis event was triggered through the extrinsic and intrinsic pathways via activation of caspases 8 and 9, respectively. Stimulation of caspase 3 and the presence of DNA ladder suggested downstream apoptotic signalling were initiated. Further confirmation of apoptosis was conducted at the molecular levels where up-regulation in Bax, as well as down-regulation of Bcl-2, Hsp-70 and survivin were observed. Plagioneurin B was also seen to arrest CAOV-3 cells cycle at the G2/M phase. Docking simulation of plagioneurin B with CD95 demonstrated that the high binding affinity and hydrogen bonds formation may explain the capability of plagioneurin B to trigger apoptosis. This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment.
Key indicator tools for shallow slope failure assessment using soil chemical property signatures and soil colour variables

Othman R, Hasni SI, Baharuddin ZM, Hashim KSH, Mahamod LH

Environ Sci Pollut Res Int, 2017 Oct;24(29):22861-22872.
PMID: 28721625 DOI: 10.1007/s11356-017-9715-9

Slope failure has become a major concern in Malaysia due to the rapid development and urbanisation in the country. It poses severe threats to any highway construction industry, residential areas, natural resources and tourism activities. The extent of damages that resulted from this catastrophe can be lessened if a long-term early warning system to predict landslide prone areas is implemented. Thus, this study aims to characterise the relationship between Oxisols properties and soil colour variables to be manipulated as key indicators to forecast shallow slope failure. The concentration of each soil property in slope soil was evaluated from two different localities that consist of 120 soil samples from stable and unstable slopes located along the North-South Highway (PLUS) and East-West Highway (LPT). Analysis of variance established highly significant difference (P

Filters

Please provide feedback to Administrator ([email protected])

External Links