Khalili, Nur Sarah Dyana (2024) Synthesis, Biological Activity And Molecular Docking Of Imidazole-Phenazine Derivatives As Potential Inhibitors For Ns2b-Ns3 Dengue Protease. Masters thesis, Perpustakaan Hamzah Sendut.
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Abstract
Dengue is a serious mosquito-borne viral infection that poses a significant global health threat, resulting in approximately half a million deaths annually. The ns2b-ns3 protease plays a crucial role in viral replication and maturation. In this study, a series of imidazole-phenazine derivatives were synthesised via condensation of benzaldehyde derivatives and 2,3-diaminophenazine, forming intermediate schiff bases, followed by air oxidation to induce in situ cyclodehydrogenation. Fifteen compounds were successfully synthesised with yields ranging from 15% to 90%. Spectroscopic techniques, including 1d and 2d nmr, ft-ir, and hrms, were used to elucidate their structures. The compounds were screened for biological activity against denv2 ns2b-ns3 protease using an in vitro assay with the fluorogenic substrate boc-gly-arg-arg-amc. Six derivatives (64b, 64e, 64f, 64g, 64k, and 64m) showed better inhibition of dengue protease, with ic50 values between 54.8 μm and 92.7 μm, compared to quercetin (ic50 = 104.8 μm). The nitro derivative, 2-(3-hydroxy-4-nitrophenyl)-1h-imidazo[4,5-b]phenazine (64f), was the most effective, with an ic50 of 54.8 μm. In silico studies using autodock vina further supported the experimental results, revealing better binding affinities for the six active derivatives, with free binding energies ranging from -8.03 to -8.50 kcal/mol, compared to quercetin (-7.20 kcal/mol). These findings suggest that the synthesised compounds hold promise as potential anti-dengue agents.
| Item Type: | Thesis (Masters) |
|---|---|
| Subjects: | R Medicine > R Medicine (General) > R735-854 Medical education. Medical schools. Research |
| Divisions: | Institut Farmaseutikal & Nutraseutikal Malaysia (Malaysian Institute of Pharmaceuticals & Nutraceuticals > Thesis |
| Depositing User: | Mr Hasmizar Mansor |
| Date Deposited: | 25 Feb 2026 01:24 |
| Last Modified: | 25 Feb 2026 01:24 |
| URI: | http://eprints.usm.my/id/eprint/63653 |
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