Displaying publications 21 - 40 of 152 in total

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  1. 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*
  2. 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.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  3. A bioactive cycloartane triterpene from Garcinia hombroniana
    Jamila N, Khan N, Khan I, Khan AA, Khan SN
    Nat Prod Res, 2016 Jun;30(12):1388-97.
    PMID: 26158779 DOI: 10.1080/14786419.2015.1060594
    The dichloromethane bark extract of Garcinia hombroniana yielded one new cycloartane triterpene; (22Z,24E)-3β-hydroxycycloart-14,22,24-trien-26-oic acid (1) together with five known compounds: garcihombronane G (2), garcihombronane J (3), 3β acetoxy-9α-hydroxy-17,14-friedolanostan-14,24-dien-26-oic acid (4), (22Z, 24E)-3β, 9α-dihydroxy-17,14-friedolanostan-14,22,24-trien-26-oic acid (5) and 3β, 23α-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid (6). Their structures were established by the spectral techniques of NMR and ESI-MS. These compounds together with some previously isolated compounds; garcihombronane B (7), garcihombronane D (8) 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone (9), volkensiflavone (10), 4''-O-methyll-volkensiflavone (11), volkensiflavone-7-O-glucopyranoside (12), volkensiflavone-7-O-rhamnopyranoside (13), Morelloflavone (14), 3''-O-methyl-morelloflavone (15) and morelloflavone-7-O-glucopyranoside (16) were evaluated for cholinesterase enzymes inhibitory activities using acetylcholinesterase and butyrylcholinesterase. In these activities, compounds 1-9 showed good dual inhibition on both the enzymes while compounds 10-16 did not reasonably contribute to both the cholinesterases inhibitory effects.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  4. Probing the characteristics and biofunctional effects of disease-affected cells and drug response via machine learning applications
    Mudali D, Jeevanandam J, Danquah MK
    Crit Rev Biotechnol, 2020 Nov;40(7):951-977.
    PMID: 32633615 DOI: 10.1080/07388551.2020.1789062
    Drug-induced transformations in disease characteristics at the cellular and molecular level offers the opportunity to predict and evaluate the efficacy of pharmaceutical ingredients whilst enabling the optimal design of new and improved drugs with enhanced pharmacokinetics and pharmacodynamics. Machine learning is a promising in-silico tool used to simulate cells with specific disease properties and to determine their response toward drug uptake. Differences in the properties of normal and infected cells, including biophysical, biochemical and physiological characteristics, plays a key role in developing fundamental cellular probing platforms for machine learning applications. Cellular features can be extracted periodically from both the drug treated, infected, and normal cells via image segmentations in order to probe dynamic differences in cell behavior. Cellular segmentation can be evaluated to reflect the levels of drug effect on a distinct cell or group of cells via probability scoring. This article provides an account for the use of machine learning methods to probe differences in the biophysical, biochemical and physiological characteristics of infected cells in response to pharmacokinetics uptake of drug ingredients for application in cancer, diabetes and neurodegenerative disease therapies.
    Matched MeSH terms: Drug Evaluation, Preclinical*
  5. An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin
    Singh I, Nair RS, Gan S, Cheong V, Morris A
    Pharm Dev Technol, 2019 Apr;24(4):448-454.
    PMID: 30084268 DOI: 10.1080/10837450.2018.1509347
    The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  6. Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia Jack
    Ang HH, Ngai TH
    Fundam Clin Pharmacol, 2001 Aug;15(4):265-8.
    PMID: 11564133 DOI: 10.1046/j.1472-8206.2001.00038.x
    The aphrodisiac effect of Eurycoma longifolia Jack (0.5 g/kg) was evaluated in noncopulator male rats using an electrical cage. Fractions of E. longifolia Jack decreased the hesitation time of noncopulator male rats, throughout the investigation period. Furthermore, it possessed a transient increase in the percentage of the male rats responding to the right choice, more than 50% of the male rats scored "right choice" after 3 weeks post-treatment and the effect became more prominent after 8 weeks post-treatment (only 40-50% of the control male rats responded to the right choice) using the electrical copulation cage. Hence, this study lends further support to the use of the plant by indigenous populations as a traditional medicine for its aphrodisiac property.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  7. Design, synthesis, in vitro cytotoxicity evaluation and structure-activity relationship of goniothalamin analogs
    Mohideen M, Zulkepli S, Nik-Salleh NS, Zulkefeli M, Weber JF, Weber JF, et al.
    Arch Pharm Res, 2013 Jul;36(7):812-31.
    PMID: 23543632 DOI: 10.1007/s12272-013-0099-1
    A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5-(hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 μM). Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  8. In vitro and in vivo evaluation of self-microemulsifying drug delivery system of buparvaquone
    Venkatesh G, Majid MI, Mansor SM, Nair NK, Croft SL, Navaratnam V
    Drug Dev Ind Pharm, 2010 Jun;36(6):735-45.
    PMID: 20136493 DOI: 10.3109/03639040903460446
    The aim of this study was to prepare a lipid-based self-microemulsifying drug delivery system (SMEDDS) to increase the solubility and oral bioavailability of a poorly water-soluble compound, buparvaquone (BPQ).
    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  9. Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system
    Haseeb MT, Hussain MA, Bashir S, Ashraf MU, Ahmad N
    Drug Dev Ind Pharm, 2017 Mar;43(3):409-420.
    PMID: 27808567 DOI: 10.1080/03639045.2016.1257017
    CONTEXT: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.

    OBJECTIVE: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.

    MATERIALS AND METHODS: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.

    RESULTS: LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.

    DISCUSSION: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.

    CONCLUSIONS: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

    Matched MeSH terms: Drug Evaluation, Preclinical/methods
  10. 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
  11. A screening method for cardiovascular active compounds in marine algae
    Agatonovic-Kustrin S, Kustrin E, Angove MJ, Morton DW
    J Chromatogr A, 2018 May 18;1550:57-62.
    PMID: 29615323 DOI: 10.1016/j.chroma.2018.03.054
    The interaction of bioactive compounds from ethanolic extracts of selected marine algae samples, separated on chromatographic plates, with nitric/nitrous acid was investigated. The nature of bioactive compounds in the marine algae extracts was characterised using UV absorption spectra before and after reaction with diluted nitric acid, and from the characteristic colour reaction after derivatization with anisaldehyde. It was found that diterpenes from Dictyota dichotoma, an edible brown algae, and sterols from green algae Caulerpa brachypus, bind nitric oxide and may act as a nitric oxide carrier. Although the carotenoid fucoxanthin, found in all brown marine algae also binds nitric oxide, the bonds between nitrogen and the fucoxanthin molecule are much stronger. Further studies are required to evaluate the effects of diterpenes from Dictyota dichotoma and sterols from green algae Caulerpa brachypus to see if they have beneficial cardiovascular effects. The method reported here should prove useful in screening large numbers of algae species for compounds with cardiovascular activity.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods*
  12. Evaluation of antiangiogenic and antoxidant properties of Parkia speciosa Hassk extracts
    Aisha AF, Abu-Salah KM, Alrokayan SA, Ismail Z, Abdulmajid AM
    Pak J Pharm Sci, 2012 Jan;25(1):7-14.
    PMID: 22186303
    Parkia speciosa Hassk is a traditional medicinal plant with strong antioxidant and hypoglycemic properties. This study aims to investigate the total phenolic content, antioxidant, cytotoxic and antiangiogenic effect of eight extracts from P. speciosa empty pods. The extracts were found to contain high levels of total phenols and demonstrated strong antioxidant effect in DPPH scavenging test. In rat aortic rings, P. speciosa extracts significantly inhibited the microvessel outgrowth from aortic tissue explants by more than 50%. The antiangiogenic activity was further confirmed by tube formation on matrigel matrix involving human endothelial cells. Cytotoxic effect was evaluated by XTT test on endothelial cells as a model of angiogenesis versus a panel of human cancer and normal cell lines. Basically the extracts did not show acute cytotoxicity. Morphology examination of endothelial cells indicated induction of autophagy characterized by formation of plenty of cytoplasmic vacuoles. The extracts were found to work by decreasing expression of vascular endothelial growth factor in endothelial cells.
    Matched MeSH terms: Drug Evaluation, Preclinical/methods; Drug Evaluation, Preclinical/statistics & numerical data
  13. Fulltext Challenges and future perspectives for 3D cerebral organoids as amodel for complex brain disorders
    Cheah, Pike-See, Mason, John O., Ling, King-Hwa
    Neuroscience Research Notes, 2019;2(1):1-6.
    MyJurnal
    The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patternsof neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally.Studying the underlying mechanisms responsible for neurologicalor neurodegenerativedisorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitationsof existing biological/animal models. Recently,cerebral organoids havebeen proposed as apromisingand revolutionary model for understanding complex brain disorders and preclinical drug screening.
    Matched MeSH terms: Drug Evaluation, Preclinical
  14. Sub-structure-based screening and molecular docking studies of potential enteroviruses inhibitors
    James SA, Yam WK
    Comput Biol Chem, 2021 Jun;92:107499.
    PMID: 33932782 DOI: 10.1016/j.compbiolchem.2021.107499
    Rhinoviruses (RV), especially Human rhinovirus (HRVs) have been accepted as the most common cause for upper respiratory tract infections (URTIs). Pleconaril, a broad spectrum anti-rhinoviral compound, has been used as a drug of choice for URTIs for over a decade. Unfortunately, for various complications associated with this drug, it was rejected, and a replacement is highly desirable. In silico screening and prediction methods such as sub-structure search and molecular docking have been widely used to identify alternative compounds. In our study, we have utilised sub-structure search to narrow down our quest in finding relevant chemical compounds. Molecular docking studies were then used to study their binding interaction at the molecular level. Interestingly, we have identified 3 residues that is worth further investigation in upcoming molecular dynamics simulation systems of their contribution in stable interaction.
    Matched MeSH terms: Drug Evaluation, Preclinical
  15. Fulltext Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic
    Khalifa SAM, Yosri N, El-Mallah MF, Ghonaim R, Guo Z, Musharraf SG, et al.
    Phytomedicine, 2021 May;85:153311.
    PMID: 33067112 DOI: 10.1016/j.phymed.2020.153311
    BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge.

    METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar).

    RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab.

    CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.

    Matched MeSH terms: Drug Evaluation, Preclinical
  16. Liver Extracellular Matrix-Based Nanofiber Scaffolds for the Culture of Primary Hepatocytes and Drug Screening
    Vasudevan A, Majumder N, Sharma I, Kaur I, Sundarrajan S, Venugopal JR, et al.
    ACS Biomater Sci Eng, 2023 Nov 13;9(11):6357-6368.
    PMID: 37847169 DOI: 10.1021/acsbiomaterials.3c01216
    Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 μm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.
    Matched MeSH terms: Drug Evaluation, Preclinical
  17. Fulltext Identification of Pyrazole Derivatives of Usnic Acid as Novel Inhibitor of SARS-CoV-2 Main Protease Through Virtual Screening Approaches
    Roney M, Singh G, Huq AKMM, Forid MS, Ishak WMBW, Rullah K, et al.
    Mol Biotechnol, 2024 Apr;66(4):696-706.
    PMID: 36752937 DOI: 10.1007/s12033-023-00667-5
    The infection produced by the SARS-CoV-2 virus remains a significant health crisis worldwide. The lack of specific medications for COVID-19 necessitates a concerted effort to find the much-desired therapies for this condition. The main protease (Mpro) of SARS-CoV-2 is a promising target, vital for virus replication and transcription. In this study, fifty pyrazole derivatives were tested for their pharmacokinetics and drugability, resulting in eight hit compounds. Subsequent molecular docking simulations on SARS-CoV-2 main protease afforded two lead compounds with strong affinity at the active site. Additionally, the molecular dynamics (MD) simulations of lead compounds (17 and 39), along with binding free energy calculations, were accomplished to validate the stability of the docked complexes and the binding poses achieved in docking experiments. Based on these findings, compound 17 and 39, with their favorable projected pharmacokinetics and pharmacological characteristics, are the proposed potential antiviral candidates which require further investigation to be used as anti-SARS-CoV-2 medication.
    Matched MeSH terms: Drug Evaluation, Preclinical
  18. Fulltext A cell-based screening system for anti-influenza A virus agents
    Wong WY, Loh SW, Ng WL, Tan MC, Yeo KS, Looi CY, et al.
    Sci Rep, 2015;5:8672.
    PMID: 25728279 DOI: 10.1038/srep08672
    Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
    Matched MeSH terms: Drug Evaluation, Preclinical*
  19. 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*
  20. 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
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