Browsing by Author "Sooriyawansha, A. M. S. C."

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In silico ADMET analysis of compounds identified in the genus Impatiens in oral administration
(Faculty of Science, University of Kelaniya Sri Lanka, 2023) Jayaweera, W. P. B. R. T.; Sooriyawansha, A. M. S. C.; Weerakoon, W. M. T. D. N.; Abeykoon, A. M. D. M. B.
New drug discovery and development avenues have opened up due to the rapid advancement of computational methodologies and technologies. Impatiens is a genus of flowering plants in the family Balsaminaceae that has a long history of traditional usage in folk medicine and cultural traditions. Although prior studies have been conducted on the phytochemical compounds of Impatiens species, there is limited information available about their pharmacokinetics and oral toxicity. Thus, the purpose of this study is to analyze the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of compounds identified in the genus Impatiens, in silico. Due to the time-consuming and costly nature of traditional experimental methods, in silico approaches are required to screen and prioritize potential candidates. Sixteen (16) compounds from the genus Impatiens were chosen to evaluate the ADMET and physicochemical properties using the in silico online tools, pkCSM, and Molinspiration. As a standard for comparison, Colchicine was used as the negative control as it is a known toxic compound. Molinspiration results showed that all the compounds, except for Esculin, followed Veber’s rule. Conversely, all compounds including Esculin adhered the Lipinski’s rule. Additionally, pkCSM results indicated Caffeic acid, Sinapinic acid, (R)-(-)-Linalool as promising candidates for oral drug administration because of their advantageous ADMET profiles and non-toxic properties. On the other hand, compounds such as Esculetin, Scopoletin, Esculin, and 2-methyl-1,4- naphthoquinone, were classified as toxic compounds since they had unfavorable ADMET profiles and exhibited Low LD50 values, hepatotoxic and mutagenic properties. R)-(-)-Linalool emerged as the phytochemical with the greatest potential for the development of oral drugs, meeting the crucial requirements outlined by Veber's and Lipinski's rules. Remarkably, it showcases outstanding attributes, including high intestinal absorption (93.163%), impressive Blood-brain barrier permeation (0.598 logBB), notable Caco2 permeability (1.493 log Papp in 10-6 cm/s), favorable water solubility (-2.612 log mol/L), significant fraction unbound (0.484 Fu), a high LD50 (2.024 mol/kg), and no inhibition of CYP450 enzymes. Additionally, it demonstrated nonmutagenic and non-hepatotoxic properties. Nonetheless, further in vivo and in vitro studies are required to promote R)-(-)-Linalool as a promising oral medication candidate. These experimental studies will assure the chemical compound’s effectiveness, security, and possible applicability for therapeutic usage in humans.
In vivo and in silico analysis of inhibition of rice (Oryza sativa) bran lipase with guava leaf (Psidium guineense swartz) extract
(Faculty of Science, University of Kelaniya Sri Lanka, 2023) Sooriyawansha, A. M. S. C.; Munaweera, R.; Jayathilaka, N.; Seneviratne, K. N.
Rice (Oryza sativa) bran (RB) is one of the most important co-products in the rice milling industry. It is frequently utilized in animal feed or discarded as waste. After milling, the majority of RB cells are ruptured, and the bran layer is removed from the endosperm. Due to that, the RB lipids encounter highly reactive rice bran lipase (RBL) enzymes which hydrolyze the RB lipids into free fatty acids. Hence RB has a short shelf life. This is the major drawback of using RB as an animal feedstock. This study focused on inhibiting the RBL activity using natural potent inhibitors and determining the mechanism of inhibition to increase the shelf life of RB. The RBLs were isolated by ion-exchange chromatography at pH 10.0 buffer. Guava (Psidium guineense swartz) leaf ethanol: water extracts were tested for inhibition of RBLs. Orlistat, a human gastric and pancreatic lipase inhibitor was used as a positive control. The percent RBLs inhibitory activities were assessed using phenyl acetate assay and the guava leaf ethanol: water extract inhibited the RBL activity (47.81% ± 9.44%). The in vivo data were validated by computational analysis. Homology-modeling of RBLs size in 40 kDa and 32 kDa, and molecular docking (AUTODOCK4) were carried out with the lactone orlistat to determine the best docking poses with the lowest estimated Gibbs free energy values (ΔG) for the mechanism of inhibition. Orlistat lactone ring carbon bound covalently to the serine residue in the characteristic GXSXG pentapeptide sequence (where X=any amino acid) in the catalytic site of the RBLs enzyme. Therefore, lactones present in guava leaf ethanol: water extract has the potential to inhibit the activity of RBLs with a similar mechanism of orlistat. Our finding suggests that guava leaf ethanol: water extract can be applied as a natural solution to increase the shelf life of RB.