Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy(Elsevier, 2022) Poddar, N.K.; Agrawal, D.; Agrawal, Y.; Wijayasinghe, Y.S.; Mukherjee, A.; Khan, S.Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.Item A Comprehensive biological and synthetic perspective on 2-Deoxy-d-Glucose (2-DG), A sweet molecule with therapeutic and diagnostic potentials(American Chemical Society, 2022) Wijayasinghe, Y.S.; Bhansali, M.P.; Borkar, M.R.; Chaturbhuj, G.U.; Muntean, B.S.; Viola, R.E.; Bhansali, P.R.Glucose, the primary substrate for ATP synthesis, is catabolized during glycolysis to generate ATP and precursors for the synthesis of other vital biomolecules. Opportunistic viruses and cancer cells often hijack this metabolic machinery to obtain energy and components needed for their replication and proliferation. One way to halt such energy-dependent processes is by interfering with the glycolytic pathway. 2-Deoxy-d-glucose (2-DG) is a synthetic glucose analogue that can inhibit key enzymes in the glycolytic pathway. The efficacy of 2-DG has been reported across an array of diseases and disorders, thereby demonstrating its broad therapeutic potential. Recent approval of 2-DG in India as a therapeutic approach for the management of the COVID-19 pandemic has brought renewed attention to this molecule. The purpose of this perspective is to present updated therapeutic avenues as well as a variety of chemical synthetic strategies for this medically useful sugar derivative, 2-DG.Item Natural products: A rich source of antiviral drug lead candidates for the management of COVID-19(Bentham Science Publishers, 2021) Wijayasinghe, Y.S.; Bhansali, P.; Viola, R.E.; Kamal, M.A.; Poddar, N.K.ABSTRACT: Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the prevention or treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-β-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anti-coronaviral research that has been published during last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies. KEYWORDS: COVID-19; Coronavirus; Natural products; Phytochemicals; SARS-CoV-2; Traditional Medicine.Item Fungal pretreatment to enhance the yield of phytochemicals and evaluation of α-amylase and α-glucosidase inhibition using Cinnamomum zeylanicum (L.) quills pressurized water extracts(Blackwell Scientific Publications, 2021) Wariyapperuma, W.A.N.M.; Kannangara, S.; Wijayasinghe, Y.S.; Subramanium, S.; Jayawardena, B.ABSTRACT: Bioactive compounds entrapped in plant materials can be effectively recovered using fungal enzymes. Cinnamomum zeylanicum Sri Wijaya (SW) and Sri Gemunu (SG) accessions and commercially available C. zeylanicum (CC) were subjected to fungal pretreatment and extracted with pressured water (PWE, 0·098 MPa). Thirteen fungal species were isolated and the substrate utilization ability of the species was tested using cellulose, pectin and lignin (indirectly). Total phenolic content (TPC, Folin-Ciocalteu method), proanthocyanidin content (PC, vanillin method) and α-amylase and α-glucosidase inhibitory potential of the extracts were evaluated. The anti-diabetic drug, Acarbose was used as the positive control. Trichoderma harzianum (MH298760) showed the highest cell lysis ability and hence was used for the microbial pretreatment process. Extracts of SW treated with T. harzianum species (Pre-SW) gave the highest percentage yield (4·08% ± 0·15%), significantly potent inhibition (P < 0·05) of α-amylase and α-glucosidase activities (IC50 57 ± 8 and 36 ± 8 μg ml-1 respectively), TPC (2·24 ± 0·02 mg gallic acid equivalent g-1 ), and PC (48·2 ± 0·4 mg of catechin equivalent g-1 ) compared to Pre-SG, Pre-CC and nontreated samples. Trichoderma harzianum treatment can enhance the hypoglycaemic properties, PC and TPC of Cinnamon extracts and provide new insights into the recovery of phytochemicals. KEYWORDS: Cinnamomum zeylanicum; Trichoderma harzianum; pressured water extraction; α-amylase; α-glucosidase.Item Relationship between enzyme properties and disease progression in Canavan disease(MTP Press, 2013) Zano, S.; Wijayasinghe, Y.S.; Malik, R.; Smith, J.; Viola, R.E.Canavan disease (CD) is a fatal neurological disorder caused by defects in the gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase catalyzes the deacetylation of N-acetylaspartate to produce acetate required for fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads to the demyelination and disrupted brain development that is found in CD patients. Sixteen different clinical mutants of aspartoacylase have been cloned, expressed and purified to examine their properties and the relationship between enzyme properties and disease phenotype. In contrast to numerous cell culture studies that reported virtually complete loss of function, each of these purified mutant enzymes was found to have measureable catalytic activity. However, the activities of these mutants are diminished, by as little as three-fold to greater than 100-fold when compared to the native enzyme. Many of these mutated enzyme forms show decreased thermal stability and an increased propensity for denaturation upon exposure to urea, but only four of the 16 mutants examined showed both diminished thermal and diminished conformational stability. Significantly, each of these lower stability mutants are responsible for the more severe phenotypes of CD, while patients with milder forms of CD have aspartoacylase mutants with generally high catalytic activity and with either good thermal or good conformational stability. These results suggest that the loss of catalytic function and the accumulation of N-acetylaspartate in Canavan disease is at least partially a consequence of the decreased protein stability caused by these mutations.