Displaying publications 1 - 20 of 54 in total

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  1. Acetyl- and O-alkyl- derivatives of β-mangostin from Garcinia mangostana and their anti-inflammatory activities
    Karunakaran T, Ee GCL, Ismail IS, Mohd Nor SM, Zamakshshari NH
    Nat Prod Res, 2018 Jun;32(12):1390-1394.
    PMID: 28715912 DOI: 10.1080/14786419.2017.1350666
    Pure β-mangostin (1) was isolated from the stem bark of Garcinia mangostana L. One monoacetate (2) and five O-alkylated β-mangostin derivatives (3-7) were synthesised from β-mangostin. The structures of these compounds were elucidated and determined using spectroscopic techniques such as 1D NMR and MS. The cytotoxicities and anti-inflammatory activities of these five compounds against RAW cell 264.7 were tested. The structural-activity relationship studies indicated that β-mangostin showed a significant activity against the LPS-induced RAW cell 264.7, while the acetyl- as well as the O-alkyl- β-mangostin derivatives did not give good activity. Naturally occurring β-mangostin demonstrated comparatively better anti-inflammatory activity than its synthetic counterparts.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  2. α-glucosidase inhibitors isolated from Mimosa pudica L
    Tasnuva ST, Qamar UA, Ghafoor K, Sahena F, Jahurul MHA, Rukshana AH, et al.
    Nat Prod Res, 2019 May;33(10):1495-1499.
    PMID: 29281898 DOI: 10.1080/14786419.2017.1419224
    The aim of the study was to isolate digestive enzymes inhibitors from Mimosa pudica through a bioassay-guided fractionation approach. Repeated silica gel and sephadex LH 20 column chromatographies of bioactive fractions afforded stigmasterol, quercetin and avicularin as digestive enzymes inhibitors whose IC50 values as compared to acarbose (351.02 ± 1.46 μg mL-1) were found to be as 91.08 ± 1.54, 75.16 ± 0.92 and 481.7 ± 0.703 μg mL-1, respectively. In conclusion, M. pudica could be a good and safe source of digestive enzymes inhibitors for the management of diabetes in future.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  3. Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in sepsis models
    Kassim M, Mansor M, Kamalden TA, Shariffuddin II, Hasan MS, Ong G, et al.
    Shock, 2014 Aug;42(2):154-60.
    PMID: 24667629 DOI: 10.1097/SHK.0000000000000179
    Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  4. Fulltext Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay
    Rothan HA, Zulqarnain M, Ammar YA, Tan EC, Rahman NA, Yusof R
    Trop Biomed, 2014 Jun;31(2):286-96.
    PMID: 25134897 MyJurnal
    Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  5. Cytotoxic effects of commercial wheatgrass and fiber towards human acute promyelocytic leukemia cells (HL60)
    Alitheen NB, Oon CL, Keong YS, Chuan TK, Li HK, Yong HW
    Pak J Pharm Sci, 2011 Jul;24(3):243-50.
    PMID: 21715255
    Cytotoxicity, the possible selective activity upon HL60 as well as the anti-proliferation effect of local health supplement wheatgrass and mixture of fibers were investigated in vitro using various cancerous cell line and normal blood cell culture. The IC(50) of wheatgrass-treated HL60 (17.5 ± 1.1, 12.5 ± 0.3, and 16 ± 0.5 microgram/ml for 24, 48 and 72 h, respectively) and fibers-treated HL60 (86.0 ± 5.5, 35.0 ± 2.5, and 52.5 ± 4.5 microgram/ml for 24, 48 and 72 h, respectively) showed that both extracts possessed optimum effect after 48 hours of treatment. No significant cytotoxic effect was observed on other type of cells. For trypan blue dye exclusion method, wheatgrass reduced the number of viable cells by 13.5% (±1.5), 47.1% (±3.6), and 64.9% (±2.7) after 24, 48 and 72 h exposure, respectively. Mixture of fibers reduced the number of viable cells by 36.4% (±2.3), 57.1% (±3.1), and 89.0% (±3.4) after 24, 48 and 72 h exposure, respectively, indicated that necrosis is also an alternative to the apoptotic mechanism of cell death. Annexin-V/propidium iodide staining revealed that both extracts induced apoptosis where early apoptosis had been detected concurrently with the reduction of percentage of cell viability. Cell cycle analysis revealed that in HL60, the percentage of apoptosis increased with time (wheatgrass: 16.0% ± 2.4, 45.3% ± 3.4 and 39.6% ± 4.1; mixture of fibers: 14.6% ± 1.8, 45.4% ± 2.3 and 45.9% ± 1.2) after exposure for 24, 48 and 72 h, respectively at the concentration of 100 microgram/ml and showed optimum effect at 48 hours. Thus, these health products can be a potential alternative supplement for leukaemia patients.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  6. Fulltext Ligand-based virtual screening using Bayesian networks
    Abdo A, Chen B, Mueller C, Salim N, Willett P
    J Chem Inf Model, 2010 Jun 28;50(6):1012-20.
    PMID: 20504032 DOI: 10.1021/ci100090p
    A Bayesian inference network (BIN) provides an interesting alternative to existing tools for similarity-based virtual screening. The BIN is particularly effective when the active molecules being sought have a high degree of structural homogeneity but has been found to perform less well with structurally heterogeneous sets of actives. In this paper, we introduce an alternative network model, called a Bayesian belief network (BBN), that seeks to overcome this limitation of the BIN approach. Simulated virtual screening experiments with the MDDR, WOMBAT and MUV data sets show that the BIN and BBN methods allow effective screening searches to be carried out. However, the results obtained are not obviously superior to those obtained using a much simpler approach that is based on the use of the Tanimoto coefficient and of the square roots of fragment occurrence frequencies.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  7. Drug-like and non drug-like pattern classification based on simple topology descriptor using hybrid neural network
    Wan-Mamat WM, Isa NA, Wahab HA, Wan-Mamat WM
    Annu Int Conf IEEE Eng Med Biol Soc, 2009;2009:6424-7.
    PMID: 19964424 DOI: 10.1109/IEMBS.2009.5333747
    An intelligent prediction system has been developed to discriminate drug-like and non drug-like molecules pattern. The system is constructed by using the application of advanced version of standard multilayer perceptron (MLP) neural network called Hybrid Multilayer Perceptron (HMLP) neural network and trained using Modified Recursive Prediction Error (MRPE) training algorithm. In this work, a well understood and easy excess Rule of Five + Veber filter properties are selected as the topological descriptor. The main idea behind the selection of this simple descriptor is to assure that the system could be used widely, beneficial and more advantageous regardless at all user level within a drug discovery organization.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  8. 15-deoxy-isoxeniolide-A, new diterpenoid from a bornean soft coral, Xenia sp
    Phan CS, Kamada T, Kobayashi K, Hamada T, Vairappan CS
    Nat Prod Res, 2018 Jan;32(2):202-207.
    PMID: 28691521 DOI: 10.1080/14786419.2017.1346638
    A new xenicane diterpenoid, 15-deoxy-isoxeniolide-A (1) along with four known compounds 9-deoxy-isoxeniolide-A (2), isoxeniolide-A (3), xeniolide-A (4) and coraxeniolide-B (5) were isolated from the Bornean soft coral Xenia sp. The structures of these metabolites were elucidated on the basis of spectral analysis, NMR and HRESIMS. Compound 5 showed cytotoxic activity against ATL cell line, S1T.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  9. New anti-bacterial halogenated tricyclic sesquiterpenes from Bornean Laurencia majuscula (Harvey) Lucas
    Kamada T, Phan CS, Vairappan CS
    Nat Prod Res, 2019 Feb;33(4):464-471.
    PMID: 29092618 DOI: 10.1080/14786419.2017.1396593
    Three new halogenated tricyclic sesquiterpenes, omphalaurediol (1), rhodolaurenones B (2) and C (3) were isolated together with nine known haloganated sesquiterpenes such as rhodolaurenone A (4), rhodolaureol (5), isorhodolaureol (6), (-)-laurencenone D (7), elatol (8), (+)-deschloroelatol (9), cartilagineol (10), (+)-laurencenone B (11) and 2-chloro-3-hydroxy-α-chamigren-9-one (12) from a population of Bornean red algae Laurencia majuscula. The structures of three new metabolites were determined based on their spectroscopic data (IR, 1D and 2D NMR, and MS). These compounds showed antibacterial activity against three human pathogenic bacteria (Escherichia coli, Salmonella typhi and Vibrio cholera).
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  10. Capgermacrenes D-G, new sesquiterpenoids from a Bornean soft coral, Capnella imbricata
    Phan CS, Vairappan CS
    Nat Prod Res, 2017 Apr;31(7):742-748.
    PMID: 27750446 DOI: 10.1080/14786419.2016.1241997
    Four new bicyclogermacrenes, capgermacrenes D (1) E (2) F (3) and G (4) were isolated from a population of Bornean soft coral Capnella imbricata. The structures of these metabolites were elucidated based on their nuclear magnetic resonance and high-resolution electrospray ionisation mass spectrometry spectral data. These compounds showed bacteriastatic and bacteriacidal activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  11. Fulltext Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice
    Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.
    Sci Rep, 2021 12 16;11(1):24121.
    PMID: 34916536 DOI: 10.1038/s41598-021-02961-1
    A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  12. Fulltext Evaluation of luciferase and GFP-expressing Nipah viruses for rapid quantitative antiviral screening
    Lo MK, Nichol ST, Spiropoulou CF
    Antiviral Res, 2014 Jun;106:53-60.
    PMID: 24680955 DOI: 10.1016/j.antiviral.2014.03.011
    Nipah virus (NiV) outbreaks have occurred in Malaysia, India, and Bangladesh, and the virus continues to cause annual outbreaks of fatal human encephalitis in Bangladesh due to spillover from its bat host reservoir. Due to its high pathogenicity, its potential use for bio/agro-terrorism, and to the current lack of approved therapeutics, NiV is designated as an overlap select agent requiring biosafety level-4 containment. Although the development of therapeutic monoclonal antibodies and soluble protein subunit vaccines have shown great promise, the paucity of effective antiviral drugs against NiV merits further exploration of compound libraries using rapid quantitative antiviral assays. As a proof-of-concept study, we evaluated the use of fluorescent and luminescent reporter NiVs for antiviral screening. We constructed and rescued NiVs expressing either Renilla luciferase or green fluorescent protein, and characterized their reporter signal kinetics in different cell types as well as in the presence of several inhibitors. The 50% effective concentrations (EC50s) derived for inhibitors against both reporter viruses are within range of EC50s derived from virus yield-based dose-response assays against wild-type NiV (within 1Log10), thus demonstrating that both reporter NiVs can serve as robust antiviral screening tools. Utilizing these live NiV-based reporter assays requires modest instrumentation, and circumvents the time and labor-intensive steps associated with cytopathic effect or viral antigen-based assays. These reporter NiVs will not only facilitate antiviral screening, but also the study of host cell components that influence the virus life cycle.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  13. Fulltext Life-span extension by pigmented rice bran in the model yeast Saccharomyces cerevisiae
    Sunthonkun P, Palajai R, Somboon P, Suan CL, Ungsurangsri M, Soontorngun N
    Sci Rep, 2019 12 02;9(1):18061.
    PMID: 31792269 DOI: 10.1038/s41598-019-54448-9
    Benefits of whole grains as dietary supplements and active ingredients in health products have been promoted. Despite being neglected as an agricultural byproduct of polished rice, pigmented rice bran has emerged as a promising source of natural anti-aging compounds. Indeed, the extract of red rice bran Hom Dang cultivar contained rich phenolic acids and flavonoids. It displayed high antioxidant activities in vitro and in vivo assays. Using yeast model, extract and bioactive compounds, quercetin and protocatechuic acid found in the rice bran pericarp, effectively reduced levels of intracellular reactive oxygen species (ROS), restored plasma membrane damages and prolonged life-span of pre-treated wild-yeast cells. Importantly, these molecules modulated life span-extension through a mechanism of ROS reduction that resembles to that operated under the highly conserved Tor1- and Sir2-dependent signaling pathways, with the human homologs TORC1 and SIRT1, respectively. The key longevity factors Sch9 and Rim15 kinases, Msn2/4 regulators and a novel transcription factor Asg1, the antioxidant enzymes superoxide dismutases and glutathione peroxidases played important role in mediating longevity. Yeast clearly provides an instrumental platform for rapid screening of compounds with anti-aging efficacies and advances knowledge in the molecular study of ageing.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  14. Phytochemical profile of Orthosiphon aristatus extracts after storage: Rosmarinic acid and other caffeic acid derivatives
    Chua LS, Lau CH, Chew CY, Ismail NIM, Soontorngun N
    Phytomedicine, 2018 Jan 15;39:49-55.
    PMID: 29433683 DOI: 10.1016/j.phymed.2017.12.015
    BACKGROUND: Orthosiphon aristatus (Blume) Miq. is a medicinal herb which is traditionally used for the treatment of diabetes and kidney diseases in South East Asia. Previous studies reported higher concentration of antioxidative phytochemicals, especially rosmarinic acid (ester of caffeic acid) and other caffeic acid derivatives in this plant extract than the other herbs such as rosemary and sage which are usually used as raw materials to produce rosmarinic acid supplement in the market.

    PURPOSE: The phytochemical profile of O. aristatus was investigated at different storage durations for quality comparison.

    METHODS: The phytochemicals were extracted from the leaves and stems of O. aristatus using a reflux reactor. The extracts were examined for total phenolic and flavonoid contents, as well as their antioxidant capacities, in terms of radical scavenging, metal chelating and reducing power. The phytochemical profiles were also analyzed by unsupervised principal component analysis and hierarchical cluster analysis, in relation to the factor of storage at 4 °C for 5 weeks.

    RESULTS: The leaf extract was likely to have more phytochemicals than stem extract, particularly caffeic acid derivatives including glycosylated and alkylated caffeic acids. This explains higher ratio of total phenolic content to total flavonoid content with higher antioxidant capacities for the leaf extracts. Rosmarinic acid dimer and salvianolic acid B appeared to be the major constituents, possibly contributing to the previously reported pharmacological properties. However, the phytochemical profiles were found changing, even though the extracts were stored in the refrigerator (4 °C). The change was significantly observed at the fifth week based on the statistical pattern recognition technique.

    CONCLUSION: O. aristatus could be a promising source of rosmarinic acid and its dimer, as well as salvianolic acid B with remarkably antioxidant properties. The phytochemical profile was at least stable for a month stored at 4 °C. It is likely to be a good choice of herbal tea with comparable radical scavenging activity, but lower caffeine content than other tea samples.

    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  15. Green synthesis of silver and copper nanoparticles using ascorbic acid and chitosan for antimicrobial applications
    Zain NM, Stapley AG, Shama G
    Carbohydr Polym, 2014 Nov 4;112:195-202.
    PMID: 25129735 DOI: 10.1016/j.carbpol.2014.05.081
    Silver and copper nanoparticles were produced by chemical reduction of their respective nitrates by ascorbic acid in the presence of chitosan using microwave heating. Particle size was shown to increase by increasing the concentration of nitrate and reducing the chitosan concentration. Surface zeta potentials were positive for all nanoparticles produced and these varied from 27.8 to 33.8 mV. Antibacterial activities of Ag, Cu, mixtures of Ag and Cu, and Ag/Cu bimetallic nanoparticles were tested using Bacillus subtilis and Escherichia coli. Of the two, B. subtilis proved more susceptible under all conditions investigated. Silver nanoparticles displayed higher activity than copper nanoparticles and mixtures of nanoparticles of the same mean particle size. However when compared on an equal concentration basis Cu nanoparticles proved more lethal to the bacteria due to a higher surface area. The highest antibacterial activity was obtained with bimetallic Ag/Cu nanoparticles with minimum inhibitory concentrations (MIC) of 0.054 and 0.076 mg/L against B. subtilis and E. coli, respectively.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  16. Fulltext Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses
    Zandi K, Bassit L, Amblard F, Cox BD, Hassandarvish P, Moghaddam E, et al.
    Antimicrob Agents Chemother, 2019 Jul;63(7).
    PMID: 31061163 DOI: 10.1128/AAC.00397-19
    Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  17. Fulltext Ligand-based virtual screening using Bayesian inference network and reweighted fragments
    Ahmed A, Abdo A, Salim N
    ScientificWorldJournal, 2012;2012:410914.
    PMID: 22623895 DOI: 10.1100/2012/410914
    Many of the similarity-based virtual screening approaches assume that molecular fragments that are not related to the biological activity carry the same weight as the important ones. This was the reason that led to the use of Bayesian networks as an alternative to existing tools for similarity-based virtual screening. In our recent work, the retrieval performance of the Bayesian inference network (BIN) was observed to improve significantly when molecular fragments were reweighted using the relevance feedback information. In this paper, a set of active reference structures were used to reweight the fragments in the reference structure. In this approach, higher weights were assigned to those fragments that occur more frequently in the set of active reference structures while others were penalized. Simulated virtual screening experiments with MDL Drug Data Report datasets showed that the proposed approach significantly improved the retrieval effectiveness of ligand-based virtual screening, especially when the active molecules being sought had a high degree of structural heterogeneity.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  18. Ligand expansion in ligand-based virtual screening using relevance feedback
    Abdo A, Saeed F, Hamza H, Ahmed A, Salim N
    J Comput Aided Mol Des, 2012 Mar;26(3):279-87.
    PMID: 22249773 DOI: 10.1007/s10822-012-9543-4
    Query expansion is the process of reformulating an original query to improve retrieval performance in information retrieval systems. Relevance feedback is one of the most useful query modification techniques in information retrieval systems. In this paper, we introduce query expansion into ligand-based virtual screening (LBVS) using the relevance feedback technique. In this approach, a few high-ranking molecules of unknown activity are filtered from the outputs of a Bayesian inference network based on a single ligand molecule to form a set of ligand molecules. This set of ligand molecules is used to form a new ligand molecule. Simulated virtual screening experiments with the MDL Drug Data Report and maximum unbiased validation data sets show that the use of ligand expansion provides a very simple way of improving the LBVS, especially when the active molecules being sought have a high degree of structural heterogeneity. However, the effectiveness of the ligand expansion is slightly less when structurally-homogeneous sets of actives are being sought.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  19. New fragment weighting scheme for the Bayesian inference network in ligand-based virtual screening
    Abdo A, Salim N
    J Chem Inf Model, 2011 Jan 24;51(1):25-32.
    PMID: 21155550 DOI: 10.1021/ci100232h
    Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic inference networks. The relationships between molecules and reference structures in the Bayesian network are encoded using a set of conditional probability distributions, which can be estimated by the fragment weighting function, a function of the frequencies of the fragments in the molecule or the reference structure as well as throughout the collection. The weighting function combines one or more fragment weighting schemes. In this paper, we have investigated five different weighting functions and present a new fragment weighting scheme. Later on, these functions were modified to combine the new weighting scheme. Simulated virtual screening experiments with the MDL Drug Data Report (23) and maximum unbiased validation data sets show that the use of new weighting scheme can provide significantly more effective screening when compared with the use of current weighting schemes.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  20. High-Throughput Screening Assays for Dengue Antiviral Drug Development
    Jabanathan SG, Xuan LZ, Ramanathan B
    Methods Mol Biol, 2021;2296:279-302.
    PMID: 33977455 DOI: 10.1007/978-1-0716-1358-0_17
    Dengue is an arthropod-borne viral disease that has become endemic and a global threat in over 100 countries. The increase in prevalence would require a long-term measure to control outbreaks. Sanofi Pasteur has licensed the tetravalent dengue vaccine (Dengvaxia) in certain dengue endemic countries. However, the efficacy of the vaccine is limited against certain dengue serotypes and can only be used for individuals from the age from 9 to 45 years old. Over the years, there has been intense research conducted on the development of antivirals against dengue virus (DENV) through either inhibiting the virus replication or targeting the host cell mechanism to block the virus entry. However, no approved antiviral drug against dengue is yet available. In this chapter, we describe the dengue antiviral development workflow including (i) prophylactic, (ii) virucidal, and (iii) postinfection assays that are employed in the antiviral drug screening process against DENV. Further, we demonstrate different methods that can be used to enumerate the reduction in virus foci number including foci-forming unit reduction assay (FFURA), estimation of viral RNA copy number through quantitative real-time PCR, and a high-throughput enzyme linked immunosorbent assay (ELISA)-based quantification of virus particles.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
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