Browsing by Author "Dissanayake, D. P."

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Investigation of the mechanism of C (aryl) - O and C (aryl) - N coupling in modified Ullmann condensation
(Research Symposium on Pure and Applied Sciences, 2018 Faculty of Science, University of Kelaniya, Sri Lanka, 2018) Gunathilaka, K. A. L. H.; Arulanandan, S.; Abeytunga, D. T. U.; Dissanayake, D. P.
Classical Ullmann reaction is one of the useful ways of the carbon-heteroatom bond formation. In this research, the modified Ullmann condensation reaction was used to accomplish the synthesis of N-phenylbenzylamine and benzylphenylether. Benzylamine and benzyl alcohol were used as the nucleophiles and bromobenzene as the alkyl halide. CuI was chosen as the catalyst along with L-proline and 1-10 - phenanthroline as the ligands, DMSO as the solvent and K2CO3 as the base. It was observed that benzylamine has an inhibitory effect on the reaction as the product, N-phenylbenzylamine, initially increased with increasing benzylamine concentration and then decreased. Inhibitory effect of benzylamine was more prominent at lower temperatures (i.e. below 800C). However, with increasing bromobenzene concentration, the product yield increased continuously. These effects were observed with copper (I) catalyst for both ligands. Although the reaction between benzylamine and bromobenzene was inhibited by benzylamine at high concentrations, the reaction between benzyl alcohol and bromobenzene was not inhibited by benzyl alcohol. It was observed that increasing benzyl alcohol concentration increased the yield of the product, benzylphenylether. However, it was observed that the yield of benzylphenylether initially increased with increasing bromobenzene concentration and then decreased. The same trend was observed for both ligands. Based on the above results and quantum mechanics calculations and conductivity experiments, two different pathways were proposed. In the case of the benzylamine-bromobenzene reaction, it is proposed that the C-Br bond activation occurs before benzylamine coordination to the catalytic center. Whereas in the case of the reaction of benzyl alcohol-bromobenzene, coordination of benzyl alcohol to the catalytic center occurs prior to the activation of bromobenzene.
Petchicine, a novel human DNMT enzyme inhibitor isolated from Sri Lankan medicinal plant: An in-silico approach
(Faculty of Science, University of Kelaniya, Sri Lanka, 2021) Dushanan, R.; Weerasinghe, S.; Dissanayake, D. P.; Senthilnithy, R.
The genetic information of humans has been regulating by various epigenetic mechanisms, which are stable and reversible. DNA methyltransferase (DNMT) is an enzyme that methylates the fifth carbon of the cytosine residue in DNA. Therefore, the methylated DNA interacts with the chromatins through the methyl-binding proteins, which leads to a cancer state. Many recent studies prove that inhibition of DNMT contributes to control cancer growth. Therefore, DNMT inhibitors have been considered as developed anticancer agents. The studies on the inhibition of the DNMT enzyme are an up-and-coming developing area for cancer therapy. Azacitidine is an approved DNMT inhibitor by the Food and Drug Administration. This work focuses on studying the impact of Azacitidine on the stability of the DNMT through computational techniques and, by performing the comparative study, suggest a new potent compound to inhibit the DNMT enzyme. These techniques can be used to investigate atomic-level descriptions of drug binding sites and how the DNMT inhibitors change the enzyme's active site. The crystal structure of the DNMT enzyme was downloaded from the Protein Data Bank, and the structure of Azacitidine was optimized by CBS-QB3 method using the G09W package. The non-toxic new compounds, Petchicine and Ouregidione, were obtained from the Sri Lanka flora database. The docking studies followed by molecular dynamics simulation were carried out to perform trajectory analysis. The results of RMSD, Rg, and hydrogen bond analysis are used to compare the behavior of the DNMT-Petchicine and DNMT-Ouregidione with the DNMT-Azacitidine complex in the aqueous environment. The results reveal that all the DNMT-inhibitor complexes attain a stable conformation during the simulation time. However, the results clearly show that the new compound Petchicine is more effective than the reference inhibitor Azacitidine; therefore, further investigations on Petchicine in future clinical trials would yield more promising results in the treatment of epigenetically caused cancer.