Displaying publications 1 - 20 of 32 in total

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  1. John CM, Ramasamy R, Al Naqeeb G, Dhiab Al-Nuaimi AH, Adam A
    Curr Med Chem, 2012 Aug 16.
    PMID: 22934758
    Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Metabolic changes in GDM affect fetal development and fetal glucose homeostasis. Several complications of diabetes are related to increased intracellular oxidative stress where prooxidants exceed antioxidant capacity. The present study was initiated to evaluate the effects of nicotinamide on CD4+CD25+ regulatory T cells (Tregs), proliferation of splenocytes, production of reactive oxygen species (ROS) by neutrophils and serum glucose levels. Changes in mRNA levels of two antioxidant genes in liver, viz, superoxide dismutase (SOD1) and catalase (CAT) were quantified with real-time PCR (QRT-PCR). Nicotinamide (50, 100 and 200 mg/kg) was supplemented p.o. to pregnant diabetic rats from days 6 through 20 of gestation. The highest dose enhanced expression of Tregs and increased splenocytes proliferation in both resting and lipopolysaccharide (LPS)-stimulated cells. Oxidative burst activity of neutrophils in response to phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP) or E. coli activation was reduced. mRNA expressions of superoxide dismutase (SOD) and catalase (CAT) genes were upregulated by nicotinamide. In summary, nicotinamide boosted the immune system through stimulation of adaptive immune cells with enhancement of antioxidant defences and reduced production of ROS. Serum glucose level was normalised by nicotinamide (200 mg/kg). These findings provide evidence for usage of nicotinamide as a supplement or as adjunct to therapeutic agents in gestational diabetes and in pregnant individuals with weakened immune systems.
  2. John CM, Ramasamy R, Al Naqeeb G, Al-Nuaimi AH, Adam A
    Curr Med Chem, 2012;19(30):5181-6.
    PMID: 23237188
    Gestational diabetes (GD) is a common complication during pregnancy. Metabolic changes in GD affect fetal development and fetal glucose homeostasis. The present study utilized a rat model of GD to evaluate the effects of nicotinamide on diabetic parameters; antioxidant gene expression viz, superoxide dismutase (SOD) and catalase (CAT); reactive oxygen species (ROS) production by neutrophils and enhancement of lymphocyte mediated immune response. Nicotinamide (50, 100 and 200 mg/kg) was orally supplemented to gestational diabetic rats from days 6 through 20 of gestation. After GD induction, the control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes. The same doses of nicotinamide upregulated mRNA expressions of SOD and CAT genes in liver but reduced the oxidative burst activity of neutrophils in response to phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP) or E. coli activation. Nicotinamide (100 & 200 mg/kg) supplementation also increased expression of activated T helper (CD4+CD25+) cells and induced proliferation of splenocytes. These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.
  3. 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.
  4. Anniebell S, Gopinath SCB
    Curr Med Chem, 2018;25(12):1433-1445.
    PMID: 28093984 DOI: 10.2174/0929867324666170116123633
    BACKGROUND: Research interest on the properties of polymer conjugated gold nanoparticle (GNP) in biomedicine is rapidly rising because of the extensive evidences for their unique properties. In the field of biomedicine, GNPs have been widely used because of their inertness and low levels of cytotoxicity. Therefore, when exposed to cells, they are less prone to exert damaging effects. GNPs are capable of being functionalized as desired and are ideal as they do not encourage undesired side reactions that might counter react with the intention of the functionalization. Biofouling is an occurrence that takes place at cellular and biological molecular level, binds non-specifically on the detection surface and forms a wrong output. This undesired incidence can be avoided by conjugating the surface of biomolecules with polymers. Densely packed repeating chains of polymers such as polyethylene glycol are capable of decreasing non-specific reactions. Applications of polymer conjugated GNPs in the field of biomedicine are as biosensors, delivery and therapeutic agents.

    CONCLUSION: Therefore, the properties and applications of polymer conjugated GNPs are studied widely as overviewed here.

  5. Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M
    Curr Med Chem, 2018;25(36):4785-4806.
    PMID: 28707587 DOI: 10.2174/0929867324666170712160621
    Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signalling pathway has become a target for the therapy of diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy. Human trials have demonstrated the ability to block IL-6 activity and in multicentric CD lead to durable clinical response and longer disease stabilisation. However, the efficacy of these treatments is still debatable for other cancers. New generation therapeutics in development such as Clazakizumab, Sarilumab, and soluble gp130-Fc have the additional features of improved binding affinity, better specificity with reduced adverse effects. A deeper understanding of the immunological basis of these agents, as well as of the challenges that are faced by immunotherapy-based products in clinical trials, will help select the most promising anti-IL-6/IL-6R therapies for large scale use. Concurrently, current research efforts to personalize treatments may help in the treatment of patients that would greatly benefit from IL-6 blocking therapies.
  6. Chang Y, Yeong KY
    Curr Med Chem, 2021 Mar 29.
    PMID: 33781187 DOI: 10.2174/0929867328666210329124415
    There have been intense research interests in sirtuins since the establishment of their regulatory roles in a myriad of pathological processes. In the last two decades, much research efforts have been dedicated to the development of sirtuin modulators. Although synthetic sirtuin modulators are the focus, natural modulators remain an integral part to be further explored in this area as they are found to possess therapeutic potential in various diseases including cancers, neurodegenerative diseases, and metabolic disorders. Owing to the importance of this cluster of compounds, this review gives a current stand on the naturally occurring sirtuin modulators, , associated molecular mechanisms and their therapeutic benefits.. Furthermore, comprehensive data mining resulted in detailed statistical data analyses pertaining to the development trend of sirtuin modulators from 2010-2020. Lastly, the challenges and future prospect of natural sirtuin modulators in drug discovery will also be discussed.
  7. Letchumanan I, Arshad MKM, Gopinath SCB
    Curr Med Chem, 2021;28(5):986-1002.
    PMID: 31971105 DOI: 10.2174/0929867327666200123092648
    Cardiovascular disease (CVD) has become one of the leading causes of morbidity and mortality in both men and women. According to the World Health Organization (WHO), ischemic heart disease is the major issue due to the narrowing of the coronary artery by plaque formation on the artery wall, which causes an inadequate flow of oxygen and blood to the heart and is called 'coronary artery disease'. The CVD death rate increased by up to 15% in 2016 (~17.6 million) compared to the past decade. This tremendous increment urges the development of a suitable biomarker for rapid and early diagnosis. Currently, C-reactive protein (CRP) is considered an outstanding biomarker for quick and accurate outcomes in clinical analyses. Various techniques have also been used to diagnose CVD, including surface plasmon resonance (SPR), colorimetric assay, enzyme-linked immunosorbent assay (ELISA), fluoro-immunoassays, chemiluminescent assays, and electrical measurements. This review discusses such diagnostic strategies and how current, cutting-edge technologies have enabled the development of high-performance detection methodologies. Concluding remarks have been made concerning the clinical significance and the use of nanomaterial in medical diagnostics towards nanotheranostics.
  8. Kumar R, Khan FU, Sharma A, Aziz IB, Poddar NK
    Curr Med Chem, 2021 Apr 04.
    PMID: 33820515 DOI: 10.2174/0929867328666210405114938
    There is substantial progress in artificial intelligence (AI) algorithms and their medical sciences applications in the last two decades. AI-assisted programs have already been established for remotely health monitoring using sensors and smartphones. A variety of AI-based prediction models available for the gastrointestinal inflammatory, non-malignant diseases, and bowel bleeding using wireless capsule endoscopy, electronic medical records for hepatitis-associated fibrosis, pancreatic carcinoma using endoscopic ultrasounds. AI-based models may be of immense help for healthcare professionals in the identification, analysis, and decision support using endoscopic images to establish prognosis and risk assessment of patient's treatment using multiple factors. Although enough randomized clinical trials are warranted to establish the efficacy of AI-algorithms assisted and non-AI based treatments before approval of such techniques from medical regulatory authorities. In this article, available AI approaches and AI-based prediction models for detecting gastrointestinal, hepatic, and pancreatic diseases are reviewed. The limitation of AI techniques in such disease prognosis, risk assessment, and decision support are discussed.
  9. Law CSW, Yeong KY
    Curr Med Chem, 2021;28(9):1716-1730.
    PMID: 32164502 DOI: 10.2174/0929867327666200312114223
    Alzheimer's disease (AD) is a neurodegenerative disorder that has affected millions of people worldwide. However, currently, there is no treatment to cure the disease. The AD drugs available in the market only manage the disease symptomatically and the effects are usually short-term. Thus, there is a need to look at alternatives AD therapies. This literature review aims to shed some light on the potential of repurposing antihypertensives to treat AD. Mid-life hypertension has not only been recognised as a risk factor for AD, but its relation with AD has also been well established. Hence, antihypertensives were postulated to be beneficial in managing AD. Four classes of antihypertensives, as well as their potential limitations and prospects in being utilised as AD therapeutics, were discussed in this review.
  10. Soliman AM, Sim RH, Das S, Mahakkannurauh P
    Curr Med Chem, 2021 Sep 10.
    PMID: 34514977 DOI: 10.2174/0929867328666210910154330
    There is an increase in the incidence of inflammatory eye diseases worldwide. Several dysregulated inflammatory pathways, including the NOD-like receptor protein 3 (NLRP3) inflammasome, have been reported to contribute significantly to the pathogenesis and progression of ophthalmic diseases. Although the available allopathic/conventional medicine has demonstrated effectiveness in managing eye diseases, there is an ongoing global demand for alternative therapeutics with minimal adverse drug reactions, easy availability, increase in patient-compliance, and better disease outcome. Therefore, several studies are investigating the utilization of natural products and herbal formulations in impeding inflammatory pathways, including the NLRP3 inflammasome, in order to prevent or manage eye diseases. In the present review, we highlight the recently reported inflammatory pathways with special emphasis on NLRP3 Inflammasomes involved in the development of eye diseases. Furthermore, we present a variety of natural products and phytochemicals that were reported to interfere with these pathways and their underlying mechanisms of action. These natural products represent potential therapeutic applications for the treatment of several inflammatory eye diseases.
  11. Alam F, Islam MA, Kamal MA, Gan SH
    Curr Med Chem, 2018;25(39):5395-5431.
    PMID: 27528060 DOI: 10.2174/0929867323666160813222436
    Over the years, natural products have shown success as antidiabetics in in vitro, in vivo studies and clinical trials. Because natural product-derived drugs are more affordable and effective with fewer side-effects compared to conventional therapies, pharmaceutical research is increasingly leaning towards the discovery of new antidiabetic drugs from natural products targeting pathways or components associated with type 2 diabetes mellitus (T2DM) pathophysiology. However, the drug discovery process is very lengthy and costly with significant challenges. Therefore, various techniques are currently being developed for the preclinical research phase of drug discovery with the aim of drug development with less time and efforts from natural products. In this review, we have provided an update on natural products including fruits, vegetables, spices, nuts, beverages and mushrooms with potential antidiabetic activities from in vivo, in vitro and clinical studies. Synergistic interactions between natural products and antidiabetic drugs, and potential antidiabetic active compounds from natural products are also documented to pave the way for combination treatment and new drug discovery, respectively. Additionally, a brief idea of the drug discovery process along with the challenges that arise during drug development from natural products and the methods to conquer those challenges are discussed to create a more convenient future drug discovery process.
  12. Suk KH, Gopinath SCB
    Curr Med Chem, 2017;24(30):3310-3321.
    PMID: 28464786 DOI: 10.2174/0929867324666170502122444
    BACKGROUND: Drug encapsulated nanoparticle has the potency to act as an effective antidote for various diseases. It is possible to enhance the bioavailability of drug encapsulated nanoparticle, whereby the yield is significantly higher compared to the standard formulation. The development with drug encapsulated nanoparticle has been improved drastically after demonstrating its capability of showing the enhanced thermophysical properties and stability of the drug. It is also utilized widely in cancer diagnoses, whereby the surface of the nanoparticle can be modified to enable the nanocarriers to reach the targeted location. Thus, the encapsulated nanoparticle can reveal neural stem cell differentiation due to the multifaceted nature and the biophysical cues to control the cell differentiation.

    OBJECTIVE: In this overview, different advantages of the drug encapsulated nanoparticle for the downstream applications are narrated with its appealing characteristics.

    CONCLUSION: The application of the drug encapsulated nanoparticle is unrestricted as it can be customized to the specific target cell in the living system.

  13. Khan NA, Anwar A, Siddiqui R
    Curr Med Chem, 2018 May 10.
    PMID: 29745319 DOI: 10.2174/0929867325666180510125633
    BACKGROUND: First discovered in the early 1970s, Acanthamoeba keratitis has remained a major eye infection and presents a significant threat to the public health, especially in developing countries. The aim is to present a timely review of our current understanding of the advances made in this field in a comprehensible manner and includes novel concepts and provides clear directions for immediate research priorities.

    METHOD: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field.

    RESULTS: The present review focuses on novel diagnostic and therapeutic strategies in details which can provide access to management and treatment of Acanthamoeba keratitis. This coupled with the recently available genome sequence information together with high throughput genomics technology and innovative approaches should stimulate interest in the rational design of preventative and therapeutic measures. Current treatment of Acanthamoeba keratitis is problematic and often leads to infection recurrence. Better understanding of diagnosis, pathogenesis, pathophysiology and therapeutic regimens, would lead to novel strategies in treatment and prophylaxis.

  14. Hosseini S, Muñoz-Soto RB, Oliva-Ramírez J, Vázquez-Villegas P, Aghamohammadi N, Rodriguez-Garcia A, et al.
    Curr Med Chem, 2020;27(5):719-744.
    PMID: 29956614 DOI: 10.2174/0929867325666180629124709
    In this paper, we review the history of Dengue, the mechanism of infection, the molecular characteristics and components of Dengue, the mechanism of entry to the target cells, cyclization of the genome and replication process, as well as translation of the proteins for virus assembly. The major emphasis of this work is on natural products and plant extracts, which were used for as palliative or adjuvant treatment of Dengue. This review article also summarizes the latest findings in regards to the marine products as effective drugs to target different symptoms of Dengue. Furthermore, an update on synthetic drugs for treating Dengue is provided in this review. As a novel alternative, we describe monoclonal antibody therapy for Dengue management and treatment.
  15. Arshad MK, Bin Mohamad Fathil MF, Gopinath SC, Ruslinda AR, Md Nor MN, Lam HY, et al.
    Curr Med Chem, 2016;23(37):4270-4284.
    PMID: 27719655
    Cardiovascular disease (CVD) is a major threat to global health, estimated to be the cause 30 % (17.3 million in 2008) of deaths every year, and the number of deaths caused by CVD is expected to increase further, reaching 23.3 million by 2030. Hence, there is a growing demand for simpler sample extraction, rapid screening results, and intervention of the subsequent analysis in emergency units. In this paper, we reviewed CVD biomarkers in blood- and saliva-based specimens. The history of cardiac biomarkers indicates that in the beginning, cardiac troponin I (cTnI) was a widely accepted 'gold standard' marker due to its high specificity and selectivity. Considering the advantages of salivary-based cardiac biomarkers, we examined correlations between non-invasive (salivary) and invasive (blood) diagnoses, and it was found that C-reactive protein (CRP) provides a better correlation. Despite the low abundance of salivary CRP, several reports displayed the detection limit down to pg/ml using existing technologies. Thus, salivary CRP has the potential to be used for future forefront diagnostics for the early assessment of cardiac risks.
  16. Abdullah AA, Lee YK, Chin SP, Lim SK, Lee VS, Othman R, et al.
    Curr Med Chem, 2020;27(30):4945-5036.
    PMID: 30514185 DOI: 10.2174/0929867326666181204155336
    To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.
  17. Mazlan NW, Tate R, Yusoff YM, Clements C, Edrada-Ebel R
    Curr Med Chem, 2020;27(11):1815-1835.
    PMID: 31272343 DOI: 10.2174/0929867326666190704130105
    Endophytic fungi have been explored not just for their ecological functions but also for their secondary metabolites as a new source of these pharmacologically active natural products. Accordingly, many structurally unique and biologically active compounds have been obtained from the cultures of endophytic fungi. Fusarium sp. and Lasiodiplodia theobromae were isolated from the root and stem of the mangrove plant Avicennia lanata, respectively, collected from Terengganu, Malaysia. High-resolution mass spectrometry and NMR spectroscopy were used as metabolomics profiling tools to identify and optimize the production of bioactive secondary metabolites in both strains at different growth stages and culture media. The spectral data was processed by utilizing Mzmine 2, a quantitative expression analysis software and an in house MS-Excel macro coupled with the Dictionary of Natural Products databases for dereplication studies. The investigation for the potential bioactive metabolites from a 15-day rice culture of Fusarium sp. yielded four 1,4- naphthoquinone with naphthazarin structures (1-4). On the other hand, the endophytic fungus L. theobromae grown on the 15-day solid rice culture produced dihydroisocoumarins (5-8). All the isolated compounds (1-8) showed significant activity against Trypanosoma brucei brucei with MIC values of 0.32-12.5 µM. Preliminary cytotoxicity screening against normal prostate cells (PNT2A) was also performed. All compounds exhibited low cytotoxicity, with compounds 3 and 4 showing the lowest cytotoxicity of only 22.3% and 38.6% of the control values at 100 µg/mL, respectively. Structure elucidation of the isolated secondary metabolites was achieved using 2D-NMR and HRESI-MS as well as comparison with literature data.
  18. Bukhari SNA, Tandiary MA, Al-Sanea MM, Abdelgawad MA, Chee CF, Hussain MA
    Curr Med Chem, 2021 Oct 26.
    PMID: 34702151 DOI: 10.2174/0929867328666211026120335
    LIMK1 and LIMK2 are involved in the regulation of cellular functions that depend on the dynamics of actin cytoskeleton. Disregulation of LIM kinases has been associated with diseases, such as tumor progression and metastasis, viral infection, and ocular diseases. Motivated by this, numerous studies have been carried out to discover small organic molecules capable of inhibiting LIM kinase effectively and selectively. In this review, a comprehensive survey of small organic molecules for LIM kinase inhibitors is reported, together with SAR study results, and the synthesis of these inhibitors.
  19. Wong XK, Yeong KY
    Curr Med Chem, 2021 Oct 27;28(34):7076-7121.
    PMID: 33588718 DOI: 10.2174/0929867328666210215113828
    Nucleobases represent key structural motifs in biologically active molecules, including synthetic and natural products. Molecular modifications made on nucleobases or their isolation from natural sources are being widely investigated for the development of drugs with improved potency for the treatment of different diseases, such as cancer, as well as viral and bacterial infections. This review article focuses on the nucleobase analogue drug developments of the past 20 years (2000-2020). Various pharmacological and medicinal aspects of nucleobases and their analogues are discussed. The current state and limitations are also highlighted.
  20. Hanis TM, Islam MA, Musa KI
    Curr Med Chem, 2021 Nov 07.
    PMID: 34749608 DOI: 10.2174/0929867328666211108110731
    BACKGROUND: Rapid advancement in computing technology and digital information leads to the possible use of machine learning on breast cancer.

    OBJECTIVE: This study aimed to evaluate the research output of the top 100 publications and further identify a research theme of breast cancer and machine-learning studies.

    METHODS: Databases of Scopus and Web of Science were used to extract the top 100 publications. These publications were filtered based on the total citation of each paper. Additionally, a bibliometric analysis was applied to the top 100 publications.

    RESULTS: The top 100 publications were published between 1993 and 2019. The most productive author was Giger ML, and the top two institutions were the University of Chicago and the National University of Singapore. The most active countries were the USA, Germany and China. Ten clusters were identified as both basic and specialised themes of breast cancer and machine learning.

    CONCLUSION: Various countries demonstrated comparable interest in breast cancer and machine-learning research. A few Asian countries, such as China, India and Singapore, were listed in the top 10 countries based on the total citation. Additionally, the use of deep learning and breast imaging data was trending in the past 10 years in the field of breast cancer and machine-learning research.

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