Browsing by Author "Dahanayake, J.N."

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Computational investigation of anti-Alzheimer effects of Asiatic acid present in Centella asiatica (Gotukola) and its derivatives
(Faculty of Science, University of Kelaniya, Sri Lanka, 2020) Fernando, R.D.M.N.,; Dahanayake, J.N.
Centella asiatica (Gotukola) is a commonly used medicinal plant that has a wide range of beneficial effects such as antioxidant effects, anti-Alzheimer's disease effects, anti-inflammatory effects, anti-fertility effects, anti-tumor effect and antimicrobial effects. Asiatic acid, pentacyclic triterpenoid is one of the secondary metabolites present in Centella asiatica extract that has all the above pharmacological properties. In this study, the Anti- Alzheimer biological activities of Asiatic acid and its derivatives were mainly focused. Alzheimer’s disease (AD) is a neurodegenerative disease. It results in loss of cognitive activity and memory and creates impairments in signaling among brain cells. Main proteins involved in Alzheimer’s disease are Human amyloid precursor protein (1AAP), Acetylcholine esterase (4PDE), Tau protein (2MZ7), Alzheimer’s beta-A (1IYT) and Alzheimer’s beta-A fibrils (2BEG). In this study, twenty derivatives of Asiatic acid were considered to investigate the anti-Alzheimer activity and one of cholinesterase inhibitor; Donepezil which is commonly used as a clinical drug in Alzheimer was considered as a reference compound. Initially, energy minimized structures of Asiatic acid and its derivatives were obtained using molecular mechanical calculations. Docking studies were carried out for the reference compound, Asiatic acid and suggested derivatives with Alzheimer’s disease related proteins. They were docked using Autodock4.0 to obtain their interactions with target proteins and to determine the amino acid residues in binding pockets. The binding affinities of derivatives with proteins were compared with the binding affinity of parent molecule, Asiatic acid and also with the binding affinity of the reference compound, Donepezil respectively. According to the results, several Asiatic acid derivatives have a higher binding affinity with acetylcholine esterase enzyme and some derivatives showed the high affinity with other proteins. The reasons for their highest binding affinities and further details were obtained by using molecular dynamics (MD) simulations. The parent molecule and several derivatives that have the highest affinity with each protein were then further analyzed using MD simulations. MD simulations were carried out on protein-ligand complexes for 50 ns using CHARMM36 force field. The trajectories obtained from MD simulations were used to calculate the radius of gyration (Rg), root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent accessible surface areas (SASA), and hydrogen bonding (HB). According to the Rg and RMSD results, the studied protein-ligand complexes were stable throughout simulation time. A significant number of hydrogen bonds were observed between the derivates and protein residues. Further, RMSF and HB results of derivatives were compared with the results of Asiatic acid, in order to investigate the higher binding affinities of the derivatives. The MD analysis results along with docking results indicated that the Asiatic acid derivatives with higher binding affinities according to docking studies have the potential to act as promising anti-Alzheimer agents.
Computational investigation of anti-Alzheimer properties of novel Curcumin derivatives
(Faculty of Science, University of Kelaniya, Sri Lanka, 2020) Amarasinghe, A.K.D.K.K.,; Dahanayake, J.N.
Curcumin, a naturally- occurring principal curcuminoid of turmeric has been used as a remedy in many Asian countries for the past century. Curcumin has shown remarkable results for the effect of various medical conditions such as cancers, liver diseases, heart diseases, osteoarthritis, and also diabetes. In this study, we discuss the effect of Curcumin and its newly synthesized derivatives as potential anti-Alzheimer compounds. Alzheimer’s disease (AD) is a chronic, neurodegenerative disease that can cause dementia that could affect memory, thinking, and behavior. Due to its anti-oxidant, anti-inflammatory, and lipophilic action, Curcumin can improve the cognitive functions in Alzheimer’s disease patients. There are satisfactory proofs for the effect of Curcumin on Alzheimer’s disease such as decreased Beta-amyloid plaques (the main concern regarding AD) and delayed degradation of neurons. The main proteins that are associated with Alzheimer’s disease and highly focused on this article are Amyloid Precursor protein (1AAP), Alzheimer’s Beta – A (1IYT), Alzheimer's Beta A fibrils (2BEG), Acetylcholine esterase (4PQE), and Tau protein (2MZ7). In this computational investigation, energy-optimized structures of selected eight derivatives of Curcumin and parent compound, Curcumin were obtained using DFT calculations. To secure a better understanding of binding interactions of the above-mentioned proteins with our selected derivatives and parent compound as ligands, docking studies were performed. To check the validation of docking results, Donepezil, a clinical drug that is currently used for the AD was used as a reference molecule and docking studies were performed. Among the newly synthesized derivatives, which were suggested as potential anti-Alzheimer agents, two derivatives have shown promising results with higher binding affinities for each protein, according to docking studies. The derivatives that showed the highest binding affinities were selected along with the parent compound, Curcumin for each protein for Molecular Dynamics (MD) simulations. MD simulations were performed on protein-ligand complexes for 50 ns using CHARMM36 force field. The mean radius of gyration (Rg), root mean square deviation (RMSD), root mean square fluctuation (RMSF) and solvent accessible surface areas of the binding pockets were calculated and hydrogen bond analysis (HBA) was also performed. Rg and RMSD results indicated the stability of the protein-ligand complex throughout the simulation time. HBA results showed that ligand has significant number of hydrogen bonds with the ligand. RMSF and HBA results of derivatives were compared with the results of Curcumin, in order to explain the higher binding affinities of the derivatives. The MD analysis results along with docking results reveal that the two derivatives with higher binding affinities according to docking studies have the potential to act as promising anti-Alzheimer agents.
Computational studies of antiviral properties of curry powder water extract against Norovirus infection
(Society for Conservation and Resource Development of Medicinal Plant, New Delhi, India., 2023) Weerarathne, H.K.; Sooriyawansha, A.M.S.C.; Jayawardena, P.A.S.N.P.; Kumarathunga, P.G.J.D.; Dananjaya, P.D.H.; Sandaruwan, W.A.M.; Dahanayake, J.N.; Kadigamuwa, C.C.
Curry powder is a mixture of ground spices that are typically used to enhance flavor, aroma, color, and consistency in curries. The Sri Lankan roasted curry powder “bedapu thuna paha” consists of coriander seeds (Coriandrum sativum L.), cumin seeds (Cuminum cyminum), fennel seeds (Foeniculum vulgare Mill.), cinnamon sticks (Cinnamomum zeylanicum) and curry leaves (Murraya koenigii) as the main ingredients. Norovirus (NoV) is a single-stranded RNA virus belonging to the family Caliciviridae. The P domain capsid protein of this virus plays an important role in the host immune response and receptor recognition because when protruding domain 1 binds with receptor molecules, it is easy to penetrate the host cell. Therefore, twenty potential ligands contained in the curry powder decoction, which were identified through literature review, were docked to the active site in the P domain from norovirus strain saga4 in complex with HBGA, and Mahanimbine, Mahanine, and Fenchone ligands binding energies were greater than -6.00 kcal/mol. According to these interactions between ligands and the protein, which were given binding energies greater than -6.00 kcal/mol, only the Mahanine ligand interacted with the highest number of amino acids in the binding pocket compared to the other two ligands (Asp374, His347, Gly346) and this ligand was subjected to Molecular Dynamics (MD) simulations. MD simulations were performed on the proteinligand complex for 10 ns using the CHARMM36 force field. Rg, RMSD. The RMSF results indicated the stability of the protein-ligand complex throughout the simulation time and suggested that Mahanine phytochemical may be used as a potential anti-virus agent against Norovirus.
Efficacy of methanolic extract of Zingiber officinale against seed-born fungi
(2023) Hansini, Navoda; Sooriyawansha, A.M.S.C.; Jayawardena, P.A.S.N.P.; Kumarathunga, P.G.J.D.; Dananjaya, P.D.H.; Edirisinghe, E.A.C.P.; Alwis, M.D.N.; Daranagama, D.A.; Dahanayake, J.N.; Kadigamuwa, C.C.
This study is focused on determining the efficacy of natural compounds present in Zingiber officinale methanolic plant extraction in controlling seed-born fungal pathogens Aspergillus flavus and Rhizopus oryzae. The maximum percentage inhibition of 94.01% and 90.43% was reported against. A. flavus and R. oryzae respectively for the crude extract in the poison food agar method. These results were further confirmed by computational investigation. [4] gingerol, [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-dehydroginger phytochemicals identified in the extract were docked to the active sites in chitin synthase from A. flavus and squalene epoxidase from A. flavus and R.oryzae, and to the RNA dependent RNA polymerase (RdRp) enzyme from R. oryzae. The highest binding energy (BE) (-8.12 kcal/mol) was noticed between the interactions of squalene epoxidase and [6]-dehydroginger, and this complex was subjected to Molecular Dynamic (MD) analysis. MD simulations were performed on protein-ligand complexes for 10 ns using CHARMM36 force field. The mean radius of gyration (Rg), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) were calculated and hydrogen bond analysis (HBA) was also performed. Rg and RMSD results indicated the stability of the protein-ligand complex throughout the simulation time.
Efficacy of methanolic extract of Zingiber officinale against seed-born fungi
(Society for Conservation and Resource Development of Medicinal Plant, New Delhi, India., 2023) Hansini, Navoda; Sooriyawansha, A.M.S.C.; Jayawardena, P.A.S.N.P.; Kumarathunga, P.G.J.D.; Dananjaya, P.D.H.; Edirisinghe, E.A.C.P.; Alwis, M.D.N.; Daranagama, D.A.; Dahanayake, J.N.; Kadigamuwa, C.C.
This study is focused on determining the efficacy of natural compounds present in Zingiber officinale methanolic plant extraction in controlling seed-born fungal pathogens Aspergillus flavus and Rhizopus oryzae. The maximum percentage inhibition of 94.01% and 90.43% was reported against. A. flavus and R. oryzae respectively for the crude extract in the poison food agar method. These results were further confirmed by computational investigation. [4]-gingerol, [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-dehydroginger phytochemicals identified in the extract were docked to the active sites in chitin synthase from A. flavus and squalene epoxidase from A. flavus and R.oryzae, and to the RNA dependent RNA polymerase (RdRp) enzyme from R. oryzae. The highest binding energy (BE) (-8.12 kcal/mol) was noticed between the interactions of squalene epoxidase and [6]-dehydroginger, and this complex was subjected to Molecular Dynamic (MD) analysis. MD simulations were performed on protein-ligand complexes for 10 ns using CHARMM36 force field. The mean radius of gyration (Rg), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) were calculated and hydrogen bond analysis (HBA) was also performed. Rg and RMSD results indicated the stability of the protein-ligand complex throughout the simulation time.
In vivo and in silico Antifungal Activity of Cinnamon Leaf Oil and Lemongrass Oil containing Chitosan Microcapsules against Aspergillus flavus
(2024-04) Kumarathunga, P.G.J.D.; Chathurangi, S.; Rajapaksha, R.P.S.P.; Sooriyawansha, A.M.S.C.; Jayawardena, P.A.S.N.P.; Dananjaya, P.D.H.; Alwis, M.D.N.; Kadigamuwa, C.C.; Dahanayake, J.N.; Wickramarachchi, Suranga
This study aimed to examine the potentiality of microencapsulated cinnamon leaf oil (CNO-CS-MCs) and lemongrass oil (LGO-CS-MCs) as natural fungicides against Aspergillus flavus. Oil encapsulated microcapsules were synthesized using ionotropic gelation method. Cinnamon leaf oil (CNO) and lemongrass oil (LGO) were characterized using GC-MS. A. flavus was isolated and identified using DNA sequencing. The minimum inhibitory and minimum lethal doses of oil-loaded microcapsules against A. flavus were evaluated under in vivo conditions and the results were further confirmed by in silico analysis. The major constituents of CNO and LGO were eugenol and citral, respectively. The minimum inhibitory doses of CNO-CS-MCs and LGO-CS-MCs were 5 mg and 7.5 mg, respectively. The minimum lethal dose of CNO-CS-MCs was 12.5 mg. As CNO showed considerably high antifungal activity than LGO, Computational investigations were carried out on the action of CNO against A. flavus. The highest protein-ligand interaction was observed for squalene epoxidase (SQ)-benzyl benzoate (BEN) complex with the binding energy of -7.70 kcal/mol. Molecular dynamics simulations were performed on SQ-BEN complex for 10 ns using CHARMM36 force field. The Rg, RMSD and RMSF results indicated the stabilization of the SQ-BEN complex throughout the simulation time.