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A series of new imidazole-phenazine derivatives were synthesized via a two-step process. The condensation of 2,3-diaminophenazine and benzaldehyde derivatives proceeds with intermediate formation of an aniline Schiff base, which undergoes subsequent cyclodehydrogenation in situ . The structures of the synthesized compounds were characterized by 1D and 2D NMR, FTIR and HRMS. A total of thirteen imidazole phenazine derivatives were synthesized and validated for their inhibitory activity as anti-dengue agents by an in vitro DENV2 NS2B-NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Two para-substituted imidazole phenazines, 3e and 3k , were found to be promising lead molecules for novel NS2B-NS3 protease inhibitors with IC 50 of 54.8 μM and 71.9 μM, respectively, compared to quercetin as a control (IC 50 104.8 μM). The in silico study was performed using AutoDock Vina to identify the binding energy and conformation of 3e and 3k with the active site of the DENV2 NS2B-NS3 protease Wichapong model. The results indicate better binding properties of 3e and 3k with calculated binding energies of -8.5 and -8.4 kcal mol -1 , respectively, compared to the binding energy of quercetin of -7.2 kcal mol -1 , which corroborates well with the experimental observations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5- bis ((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits' free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52-55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds' toxicity and mutagenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salin, Hariono, Khalili, Zakaria, Saqallah, Mohamad Taib, Kamarulzaman, Wahab and Khawory.)

Background and Aim: The aim of this study is to evaluate the effects of gamma radiation treatment on three medicinal plants, namely Euodia malayana, Gnetum gnemon and Khaya senegalensis at two different forms; methanol leaf extracts and dried leaves respectively., Experimental Procedure: The microbial limit test (MLT) studies indicated the suitable dosage of minimum and maximum gamma irradiation for leaf extracts as well as dried leaves of all the tested medicinal plants. Quantitative analysis of total phenolic content (TPC) analysis is based on calorimetric measurements determined using the Folin-Ciocalteu reagent with gallic acid (GA) used as the reference. In vitro cytotoxicity assay by using fibroblast (L929) cell lines was performed on each plant to determine the toxicity effect which sodium dodecyl sulfate (SDS) as the positive control. DPPH (2,2-diphenyl-1-picryl-hydrazyl) assay was conducted by using vitamin C and GA as the positive controls to determine the antioxidant property of each plant., Results and Conclusion: The MLT analysis indicated that the suitable dosage gamma irradiation for leaf extracts was 6-12 kGy and dried leaves were 9-13 kGy. The amount of GA concentration in each plant increased significantly from 30-51 mg GAE g -1 before treatment to 57-103 mg GAE g -1 after treatment with gamma radiation. This showed no significant effect of in vitro cytotoxicity activity before and after treatment with gamma irradiation in this study. Effective concentration (EC 50 ) values of Khaya senegalensis plant reduced significantly (P ≤ 0.005) from 44.510 μg/ml before treatment to 24.691 μg/ml after treatment with gamma radiation, which indicate an increase of free radical scavenging activity., Competing Interests: Declaration of competing interest There is no conflict of interest because this research is original and not publishes at other articles., (Copyright © 2019 Elsevier Ltd. All rights reserved.)