Displaying publications 41 - 60 of 162 in total

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  1. Mushroom immunomodulators: unique molecules with unlimited applications
    El Enshasy HA, Hatti-Kaul R
    Trends Biotechnol, 2013 Dec;31(12):668-77.
    PMID: 24125745 DOI: 10.1016/j.tibtech.2013.09.003
    For centuries, mushrooms have been used as food and medicine in different cultures. More recently, many bioactive compounds have been isolated from different types of mushrooms. Among these, immunomodulators have gained much interest based on the increasing growth of the immunotherapy sector. Mushroom immunomodulators are classified under four categories based on their chemical nature as: lectins, terpenoids, proteins, and polysaccharides. These compounds are produced naturally in mushrooms cultivated in greenhouses. For effective industrial production, cultivation is carried out in submerged culture to increase the bioactive compound yield, decrease the production time, and reduce the cost of downstream processing. This review provides a comprehensive overview on mushroom immunomodulators in terms of chemistry, industrial production, and applications in medical and nonmedical sectors.
    Matched MeSH terms: Drug Discovery
  2. In vivo antimalarial activity of the endophytic actinobacteria, Streptomyces SUK 10
    Baba MS, Zin NM, Hassan ZA, Latip J, Pethick F, Hunter IS, et al.
    J Microbiol, 2015 Dec;53(12):847-55.
    PMID: 26626355 DOI: 10.1007/s12275-015-5076-6
    Endophytic bacteria, such as Streptomyces, have the potential to act as a source for novel bioactive molecules with medicinal properties. The present study was aimed at assessing the antimalarial activity of crude extract isolated from various strains of actinobacteria living endophytically in some Malaysian medicinal plants. Using the four day suppression test method on male ICR strain mice, compounds produced from three strains of Streptomyces (SUK8, SUK10, and SUK27) were tested in vivo against Plasmodium berghei PZZ1/100 in an antimalarial screen using crude extracts at four different concentrations. One of these extracts, isolated from Streptomyces SUK10 obtained from the bark of Shorea ovalis tree, showed inhibition of the test organism and was further tested against P. berghei-infected mice for antimalarial activity at different concentrations. There was a positive relationship between the survival of the infected mouse group treated with 50 µg/kg body weight (bw) of ethyl acetate-SUK10 crude extract and the ability to inhibit the parasites growth. The parasite inhibition percentage for this group showed that 50% of the mice survived for more than 90 days after infection with the parasite. The nucleotide sequence and phylogenetic tree suggested that Streptomyces SUK10 may constitute a new species within the Streptomyces genus. As part of the drug discovery process, these promising finding may contribute to the medicinal and pharmaceutical field for malarial treatment.
    Matched MeSH terms: Drug Discovery*
  3. Efficient differentiation of human ES and iPS cells into cardiomyocytes on biomaterials under xeno-free conditions
    Sung TC, Liu CH, Huang WL, Lee YC, Kumar SS, Chang Y, et al.
    Biomater Sci, 2019 Oct 28.
    PMID: 31656967 DOI: 10.1039/c9bm00817a
    Current xeno-free and chemically defined methods for the differentiation of hPSCs (human pluripotent stem cells) into cardiomyocytes are not efficient and are sometimes not reproducible. Therefore, it is necessary to develop reliable and efficient methods for the differentiation of hPSCs into cardiomyocytes for future use in cardiovascular research related to drug discovery, cardiotoxicity screening, and disease modeling. We evaluated two representative differentiation methods that were reported previously, and we further developed original, more efficient methods for the differentiation of hPSCs into cardiomyocytes under xeno-free, chemically defined conditions. The developed protocol successively differentiated hPSCs into cardiomyocytes, approximately 90-97% of which expressed the cardiac marker cTnT, with beating speeds and sarcomere lengths that were similar to those of a healthy adult human heart. The optimal cell culture biomaterials for the cardiac differentiation of hPSCs were also evaluated using extracellular matrix-mimetic material-coated dishes. Synthemax II-coated and Laminin-521-coated dishes were found to be the most effective and efficient biomaterials for the cardiac differentiation of hPSCs according to the observation of hPSC-derived cardiomyocytes with high survival ratios, high beating colony numbers, a similar beating frequency to that of a healthy adult human heart, high purity levels (high cTnT expression) and longer sarcomere lengths similar to those of a healthy adult human heart.
    Matched MeSH terms: Drug Discovery
  4. Fulltext Expression, purification and characterization of the dimeric protruding domain of Macrobrachium rosenbergii nodavirus capsid protein expressed in Escherichia coli
    Chong LC, Ganesan H, Yong CY, Tan WS, Ho KL
    PLoS One, 2019;14(2):e0211740.
    PMID: 30707739 DOI: 10.1371/journal.pone.0211740
    Macrobrachium rosenbergii nodavirus (MrNV) is the causative agent of white tail disease (WTD) which seriously impedes the production of the giant freshwater prawn and has a major economic impact. MrNV contains two segmented RNA molecules, which encode the RNA dependent RNA polymerase (RdRp) and the capsid protein (MrNV-CP) containing 371 amino acid residues. MrNV-CP comprises of the Shell (S) and the Protruding (P) domains, ranging from amino acid residues 1-252 and 253-371, respectively. The P-domain assembles into dimeric protruding spikes, and it is believed to be involved in host cell attachment and internalization. In this study, the recombinant P-domain of MrNV-CP was successfully cloned and expressed in Escherichia coli, purified with an immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC) up to ~90% purity. Characterization of the purified recombinant P-domain with SEC revealed that it formed dimers, and dynamic light scattering (DLS) analysis demonstrated that the hydrodynamic diameter of the dimers was ~6 nm. Circular dichroism (CD) analysis showed that the P-domain contained 67.9% of beta-sheets, but without alpha-helical structures. This is in good agreement with the cryo-electron microscopic analysis of MrNV which demonstrated that the P-domain contains only beta-stranded structures. Our findings of this study provide essential information for the production of the P-domain of MrNV-CP that will aid future studies particularly studies that will shed light on anti-viral drug discovery and provide an understanding of virus-host interactions and the viral pathogenicity.
    Matched MeSH terms: Drug Discovery
  5. Fulltext Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity
    Han Jie L, Jantan I, Yusoff SD, Jalil J, Husain K
    Front Pharmacol, 2020;11:553404.
    PMID: 33628166 DOI: 10.3389/fphar.2020.553404
    Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The studies provided some insights on its several mechanisms of action in cancer and other disease states. However, more detail mechanistic studies are needed to understand its pharmacological effects. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery.
    Matched MeSH terms: Drug Discovery
  6. Could bacteriophages isolated from the sewage be the solution to methicillin-resistant Staphylococcus aureus?
    Tan CS, Aqiludeen NA, Tan R, Gowbei A, Mijen AB, Santhana Raj L, et al.
    Med J Malaysia, 2020 03;75(2):110-116.
    PMID: 32281590
    INTRODUCTIONS: The emergence of multidrug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) complicates the treatment of the simplest infection. Although glycopeptides such as vancomycin still proves to be effective in treating MRSA infections, the emergence of vancomycin-resistant strains limits the long term use of this antibiotic. Bacteriophages are ubiquitous bacterial viruses which is capable of infecting and killing bacteria including its antibiotic-resistant strains. Bactericidal bacteriophages use mechanisms that is distinct from antibiotics and is not affected by the antibioticresistant phenotypes.

    OBJECTIVES: The study was undertaken to evaluate the possibility to isolate bacteriolytic bacteriophages against S.aureus from raw sewage water and examine their efficacy as antimicrobial agents in vitro.

    METHODS: Bacteriophages were isolated from the raw sewage using the agar overlay method. Isolated bacteriophages were plaque purified to obtain homogenous bacteriophage isolates. The host range of the bacteriophages was determined using the spot test assay against the 25 MRSA and 36 MSSA isolates obtained from the Sarawak General Hospital. Staphylococcus saprophyticus, Staphylococcus sciuri and Staphylococcus xylosus were included as non-SA controls. The identity of the bacteriophages was identified via Transmission Electron Microscopy and genomic size analysis. Their stability at different pH and temperature were elucidated.

    RESULTS: A total of 10 lytic bacteriophages infecting S.aureus were isolated and two of them namely ΦNUSA-1 and ΦNUSA-10 from the family of Myoviridae and Siphoviridae respectively exhibited exceptionally broad host range against >80% of MRSA and MSSA tested. Both bacteriophages were specific to S.aureus and stable at both physiologic pH and temperature.

    CONCLUSION: This study demonstrated the abundance of S.aureus specific bacteriophages in raw sewage. Their high virulence against both MSSA and MRSA is an excellent antimicrobial characteristic which can be exploited for bacteriophage therapy against MRSA.

    Matched MeSH terms: Drug Discovery/methods
  7. Genome-scale metabolic models as platforms for identification of novel genes as antimicrobial drug targets
    Mienda BS, Salihu R, Adamu A, Idris S
    Future Microbiol, 2018 03;13:455-467.
    PMID: 29469596 DOI: 10.2217/fmb-2017-0195
    The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs. This approach will follow the existing protocol for construction of high-quality GEMs, which could ultimately reduce the time, cost and labor-intensive processes involved in identification of novel antimicrobial drug targets in drug discovery pipelines. We discuss the current impact of existing GEMs of selected multidrug-resistant pathogenic bacteria for identification of novel antimicrobial drug targets and the challenges of closing the gap between genome-scale metabolic modeling and conventional experimental trial-and-error approaches in drug discovery pipelines.
    Matched MeSH terms: Drug Discovery
  8. Exploring the current use of animal models in glaucoma drug discovery: where are we in 2023?
    Agarwal R, Agarwal P, Iezhitsa I
    Expert Opin Drug Discov, 2023;18(11):1287-1300.
    PMID: 37608634 DOI: 10.1080/17460441.2023.2246892
    INTRODUCTION: Animal models are widely used in glaucoma-related research. Since the elevated intraocular pressure (IOP) is a major risk factor underlying the disease pathogenesis, animal models with high IOP are commonly used. However, models are also used to represent the clinical context of glaucomatous changes developing despite a normal IOP.

    AREAS COVERED: Herein, the authors discuss the various factors that contribute to the quality of studies using animal models based on the evaluation of studies published in 2022. The factors affecting the quality of studies using animal models, such as the animal species, age, and sex, are discussed, along with various methods and outcomes of studies involving different animal models of glaucoma.

    EXPERT OPINION: Translating animal research data to clinical applications remains challenging. Our observations in this review clearly indicate that many studies lack scientific robustness not only in their experiment conduct but also in data analysis, interpretation, and presentation. In this context, ensuring the internal validity of animal studies is the first step in quality assurance. External validity, however, is more challenging, and steps should be taken to satisfy external validity at least to some extent.

    Matched MeSH terms: Drug Discovery
  9. Multi-step molecular docking and dynamics simulation-based screening of large antiviral specific chemical libraries for identification of Nipah virus glycoprotein inhibitors
    Kalbhor MS, Bhowmick S, Alanazi AM, Patil PC, Islam MA
    Biophys Chem, 2021 03;270:106537.
    PMID: 33450550 DOI: 10.1016/j.bpc.2020.106537
    Nipah virus (NiV) infections are highly contagious and can cause severe febrile encephalitis. An outbreak of NiV infection has reported high mortality rates in Southeast Asian countries including Bangladesh, East Timor, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, Philippines, Thailand and India. Considering the high risk for an epidemic outbreak, the World Health Organization (WHO) declared NiV as an emerging priority pathogen. However, there are no effective therapeutics or any FDA approved drugs available for the treatment of this infection. Among the known nine proteins of NiV, glycoprotein plays an important role in initiating the entry of viruses and attaching to the host cell receptors. Herein, three antiviral databases consisting of 79,892 chemical entities have been computationally screened against NiV glycoprotein (NiV-G). Particularly, multi-step molecular docking followed by extensive molecular binding interactions analyses, binding free energy estimation, in silico pharmacokinetics, synthetic accessibility and toxicity profile evaluations have been carried out for initial identification of potential NiV-G inhibitors. Further, molecular dynamics (MD) simulation has been performed to understand the dynamic properties of NiV-G protein-bound with proposed five inhibitors (G1-G5) and their interactions behavior, and any conformational changes in NiV-G protein during simulations. Moreover, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) based binding free energies (∆G) has been calculated from all MD simulation trajectories to understand the energy contribution of each proposed compound in maintaining and stabilizing the complex binding interactions with NiV-G protein. Proposed compounds showed high negative ∆G values ranging from -166.246 to -226.652 kJ/mol indicating a strong affinity towards the NiV-G protein.
    Matched MeSH terms: Drug Discovery
  10. Fulltext Study on the potential toxicity of a thymoquinone-rich fraction nanoemulsion in Sprague Dawley rats
    Tubesha Z, Imam MU, Mahmud R, Ismail M
    Molecules, 2013 Jun 26;18(7):7460-72.
    PMID: 23803717 DOI: 10.3390/molecules18077460
    Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.
    Matched MeSH terms: Drug Discovery
  11. A Review of Bisindolylmethane as an Important Scaffold for Drug Discovery
    Imran S, Taha M, Ismail NH
    Curr Med Chem, 2015;22(38):4412-33.
    PMID: 26438249
    Bisindolylmethane and its derivatives are pharmacologically active and applicable in the field of pharmaceutical chemistry. Bisindolylmethanes have a variety of biological activities such as antihyperglycemic, antiinflammatory, antibacterial, anticancer, and antileishmanial activities, including enzyme inhibition activity. They play a crucial role in many diseases especially anticancer activity. Modifying their structure had proven to be useful in the search of new therapeutic agents. Extensive research carried out on bisindolylmethane and its derivatives shows that they are pharmacologically significant. The present review focuses on the pharmacological profile of bisindolylmethane derivatives. This review includes the current literature with an update of research findings as well as the perspectives that they hold for future research.
    Matched MeSH terms: Drug Discovery*
  12. Fulltext In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells
    Khazaei S, Esa NM, Ramachandran V, Hamid RA, Pandurangan AK, Etemad A, et al.
    Front Pharmacol, 2017;8:5.
    PMID: 28197098 DOI: 10.3389/fphar.2017.00005
    Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract of A. atroviolaceum was found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated to Cdk1 downregulation, S phase arrest in MDA-MB-231 which is p53 and Cdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned with Cdk1 downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2. Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb of A. atroviolaceum may be useful for the treatment of cancer lonely or in combination with other drugs.
    Matched MeSH terms: Drug Discovery
  13. Recent advances in galactose-engineered nanocarriers for the site-specific delivery of siRNA and anticancer drugs
    Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, et al.
    Drug Discov Today, 2018 05;23(5):960-973.
    PMID: 29129804 DOI: 10.1016/j.drudis.2017.11.003
    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
    Matched MeSH terms: Drug Discovery
  14. Gut bacteria of animals/pests living in polluted environments are a potential source of antibacterials
    Akbar N, Siddiqui R, Sagathevan KA, Khan NA
    Appl Microbiol Biotechnol, 2019 May;103(10):3955-3964.
    PMID: 30941460 DOI: 10.1007/s00253-019-09783-2
    The morbidity and mortality associated with bacterial infections have remained significant despite chemotherapeutic advances. With the emergence of drug-resistant bacterial strains, the situation has become a serious threat to the public health. Thus, there is an urgent need to identify novel antibacterials. The majority of antibiotics available in the market are produced by bacteria isolated from soil. However, the low-hanging fruit has been picked; hence, there is a need to mine bacteria from unusual sources. With this in mind, it is important to note that animals and pests such as cockroaches, snake, crocodiles, and water monitor lizard come across pathogenic bacteria regularly, yet flourish in contaminated environments. These species must have developed methods to defend themselves to counter pathogens. Although the immune system is known to possess antiinfective properties, gut bacteria of animals/pests may also offer a potential source of novel antibacterial agents, and it is the subject of this study. This paper discusses our current knowledge of bacteria isolated from land and marine animals with antibacterial properties and to propose untapped sources for the isolation of bacteria to mine potentially novel antibiotic molecules.
    Matched MeSH terms: Drug Discovery/methods
  15. Fulltext Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii
    Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.
    Antibiotics (Basel), 2020 May 25;9(5).
    PMID: 32466210 DOI: 10.3390/antibiotics9050276
    The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.
    Matched MeSH terms: Drug Discovery
  16. The use of transgenic parasites in malaria vaccine research
    Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM
    Expert Rev Vaccines, 2017 Jul;16(7):1-13.
    PMID: 28525963 DOI: 10.1080/14760584.2017.1333426
    INTRODUCTION: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
    Matched MeSH terms: Drug Discovery/methods*
  17. Senolytics: Opening avenues in drug discovery to find novel therapeutics for Parkinson's Disease
    Kakoty V, Kalarikkal Chandran S, Gulati M, Goh BH, Dua K, Kumar Singh S
    Drug Discov Today, 2023 Jun;28(6):103582.
    PMID: 37023942 DOI: 10.1016/j.drudis.2023.103582
    Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
    Matched MeSH terms: Drug Discovery
  18. Fulltext A side-effect free method for identifying cancer drug targets
    Ashraf MI, Ong SK, Mujawar S, Pawar S, More P, Paul S, et al.
    Sci Rep, 2018 04 27;8(1):6669.
    PMID: 29703908 DOI: 10.1038/s41598-018-25042-2
    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.
    Matched MeSH terms: Drug Discovery/methods*
  19. Mechanisms of Antimicrobial Resistance (AMR) and Alternative Approaches to Overcome AMR
    Moo CL, Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, et al.
    Curr Drug Discov Technol, 2020;17(4):430-447.
    PMID: 30836923 DOI: 10.2174/1570163816666190304122219
    Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.
    Matched MeSH terms: Drug Discovery
  20. Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer
    Islam R, Lam KW
    Eur J Med Chem, 2020 Dec 01;207:112812.
    PMID: 32937283 DOI: 10.1016/j.ejmech.2020.112812
    Triple-negative breast cancer (TNBC) is the most aggressive type of cancer, with a high risk of death on recurrence. To date, there is a lack of approved targeted agents for the treatment of the disease. Patients with TNBC continue to depend on surgery, chemotherapy, and radiotherapy, all of which have a wide side effect profile. In the present review, we highlight the current progress and exciting developments in the small-molecule targeted therapy for the treatment of TNBC. Finally, we also discuss the prospect of combining targeted therapy and immunotherapy for the effective treatment of TNBC.
    Matched MeSH terms: Drug Discovery*
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