International Postgraduate Research Conference (IPRC)
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Item Computational Investigation of Antioxidant Activity of Dietary Vitamins; DFT Study(International Postgraduate Research Conference 2019, Faculty of Graduate Studies, University of Kelaniya, Sri Lanka, 2019) Jayawardana, S.B.; Pandithavidana, D.R.Among numerous types of antioxidant compounds, dietary vitamins form an important class of chain-breaking compounds which have a potential to quench reactive radical intermediates produced during the oxidative processes of both biological and commercial importance materials. According to the recent investigations, the possible role of antioxidants in prevention of human diseases has taken a leading role. Antioxidants are also capable to defend against number of disease conditions such as aging, atherosclerosis, cancer, asthma, arthritis and autoimmune diseases. Antioxidants as external supplements are used to maintain the concentration of free radicals as low as possible and to avoid the oxidative stress. They are heavily used in food industry to maintain the quality of the ready-to-eat foods, and to boost the shelf life. The computational chemistry has become a versatile tool to investigate wide range of thermodynamic properties which are hardly measurable, as well as to predict the trends between them. The efficiency of an antioxidant can be successfully estimated by analyzing the potential energy surface (PES) of the reaction with a certain radical. This potential energy surface permits calculation of the activation and reaction energies, entailing that both kinetic and thermodynamic approaches to the interested reaction are presented. As well as the computed parameters provide useful information on the radical scavenging power without considering reaction pathway. Density functional theory (DFT) was used to explore the antioxidant properties of some naturally occurring dietary vitamins, and the reaction enthalpies related to various mechanisms of primary antioxidant action, i.e., hydrogen atom transfer (HAT), single electron transfer–proton transfer (SET–PT), and sequential proton loss–electron transfer (SPLET) have been investigated in detail. B3LYP, M05-2X, and M06-2X functionals were utilized in this work. For aqueous phase studies, the integral equation formalism polarized continuum model (IEF–PCM) was employed. From the outcomes, hydrogen atom transfer (HAT) was the most probable mechanism for the antioxidant action of this class of compounds. Comparison of found results with experimental data (available in literature), vitamin C possesses the lowest enthalpy values for both proton affinity (PA) and bond dissociation energy (BDE) in the aqueous phase, suggesting it as the most promising candidate as an antioxidant. Accordingly, these computational insights encourage the design of structurally novel, simple vitamins which will be more economical and beneficial in the pharmaceutical industry.Item Molecular Docking Analysis to Elucidate the Potential Drug Action of Phytochemicals Present in Ashwagandharishta towards Memory Related Disorders(19th Conference on Postgraduate Research, International Postgraduate Research Conference 2018, Faculty of Graduate Studies,University of Kelaniya, Sri Lanka, 2018) Munaweera, R.R.K.W.; Pandithavidana, D.R.Ashwagandharishta is an Ayurveda medicine that is used to treat psychiatric conditions, dullness, memory related diseases, sluggishness, epilepsy, depression, anxiety, schizophrenia. The main plant ingredient used to prepare this is Withaniasomnifera. It contains various classes of secondary metabolites such as steroidal lactones, phytosterols, sitoindosides and alkaloids. Memory-related disorders are closely associated with the defects in cholinergic neurotransmission. Repairing mechanisms for theses defects provide promising treatment strategies for these kinds of disorders. The most abundant receptor found in cholinergic neurotransmission is nicotinic acetylcholine receptor. Alpha-7 nicotinic acetylcholine receptor is a sub type of nicotinic acetylcholine receptor and has been identified as one of the most useful drug target for the treatment of nervous system related disorders. Potential agonists of alpha-7 nicotinic acetylcholine receptor have shown to be enhancers of cognitive performance when memory related disorders are treated. Molecular docking analyses have been carried out to identify any possible secondary metabolites present in Ashwagandharishta that could act as agonists of alpha-7 nicotinic acetylcholine receptor using AutoDock4 software package. Four possible phytochemicals have been selected based on drug likeness, blood brain barrier penetrability and agonistic binding ability with the receptor. Their docked conformations, binding at correct binding site, binding energies and dissociation constants (kI) have been further investigated computationally Based on the molecular docking studies it was revealed that anaferine and anahygrine possessed lower binding energies with compared to the binding energy of nicotine while cuscohygrine showed relatively higher energy in binding. When kI (dissociation constant) values were compared, anaferine and anahygrine possessed relatively higher values than that of nicotine. According to computational studies, cuscohygrine and palletierine showed some tendency to bind nonspecifically at other sites of the receptor. However, nonspecific bindings for anaferine and anahygrine were not energetically favorable. According this computational investigation, it has been found that two phytochemicals (anaferine and anahygrine) show promising agonistic activity towards the receptor. Thus anaferine and anahygrine have high possibility to serve as alpha-7nAChR agonists which show potential drug action towards memory related disorders.Item Computational Investigation of Pesticide Induced Oxidative Stress and Its Impact on the Chronic Kidney Disease of Unknown Etiology (CKDu)(19th Conference on Postgraduate Research, International Postgraduate Research Conference 2018, Faculty of Graduate Studies,University of Kelaniya, Sri Lanka, 2018) Deshan, T.M.V.; Pandithavidana, D.R.The chronic kidney disease of unknown etiology (CKDu) has been a major health issue in Sri Lanka within the last three decades. It has been a burden problem mainly for the rural agricultural community. Many investigative efforts have been carried out to identify its unknown origin and several risk factors which have been associated. But levels of any of the pollutants or conditions reported have not been consistent or correlated with the prevalence of the disease as it is named (as the sole cause of CKDu). A possible link between oxidative stress and the progression of the disease has been identified. The environmental factors which favor the development of oxidative stress are prevalent in those affected areas. The study of “pesticide induced oxidative stress” has been a topic of research interest. Alterations in the balance between the production of free radicals and the antioxidant defenses were recognized as one of the main causes. The secondary interactions between small ligands and macromolecules were computationally investigated using AutoDock molecular docking program. In this computational study, four major pesticides were docked with different enzymes which directly related to mechanisms in generating oxidative stress. The strength of the binding of the pesticide in the binding site of the corresponding enzyme was used to emphasize its potential interaction with the enzyme. According to molecular docking investigations, it was evident that three organophospahates; Profenofos, Diazinon and Chlrofyrifos possessed relatively similar binding energies at the active site compared to the inducer for Cytochrome P450 A34 enzyme. Profenofos showed the lowest Gibbs binding energy among three. The computational studies predicted that these pesticides might serve as potent inducers or substrates for the enzyme. Imidacloprid was not metabolized by the enzyme as it didn’t show any interactions at the active site. None of the pesticides would act as a potent inhibitor of the enzyme. Further, computational simulations revealed that these organophosphates behaved as potent enzyme inducers as well as substrates which involved in bio activation. These computed results directed to a feasible mechanism to disclose how reactive oxygen species were generated to cause oxidative stress. The location of binding pocket and the strength of binding at the active site of the enzyme were important parameters used to generate these predictions. This computational study has been utilized to predict mechanistic steps related to the “pesticide induced oxidative stress” which is a causative factor for the multi factorial origin of CKDu.