A. El-Ghorab

This work addresses two research topics: the first concerns the specific/sensitive trapping of hydroxyl radicals (•OH), and the second concerns the efficacy of encapsulating natural antioxidants, potentially lengthening their preservation activity. For context, nano-titania was solar-irradiated to produce •OH, which was spectrofluorimetrically assessed, based on the selective aromatic hydroxylation of the non-fluorescent sodium terephthalate to 2-hydroxyterephthalate fluorophore. Fluorescence intensity is proportional to generated •OH. Thus, a simple/rapid indirect method was utilized to assess •OH precisely. Accordingly, novel photoluminescent system is outlined in order to assess the scavenging potentiality of •OH in date seed oil (DSO) in both its pure and encapsulated formulations (ECP–DSO), i.e., when fresh and 5 months after extraction and encapsulation, respectively. With the addition of 80 μg/mL DSO or ECP–DSO, the efficacy of •OH scavenging amounted to 25.12 and 63.39%, which increased to 68.65 and 92.72% when 200 μg/mL DSO or ECP–DSO, respectively, was added. Moreover, the IC50 of DSO and ECP–DSO is 136.6 and 62.1 µg/mL, respectively. Furthermore, DSO and ECP–DSO decreased the kinetics for producing •OH by ≈20 and 40%, respectively, relative to •OH generated in the absence of antioxidant. This demonstrates the benefits of encapsulation on the preservation activity of natural antioxidants, even after five months after extraction, in terms of its interesting activity when compared to synthetic antioxidants. The developed fluorimetric •OH probing upgrades antioxidant medicines, thus paving the way for theoretical/practical insights on mechanistic hydroxyl radical-damaging biology.

COVID-19 infection is now considered one of the leading causes of human death. As an attempt towards the discovery of novel medications for the COVID-19 pandemic, nineteen novel compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed and synthesized via a click reaction based on our previous work. The novel compounds were assessed using an in vitro effect on the growth of SARS-CoV-2 virus-infested Vero cells with different compound concentrations: 1 and 10 μM. The data revealed that most of these derivatives showed potent cellular anti-COVID-19 activity and inhibited viral replication by more than 50% with no or weak cytotoxic effect on harboring cells. In addition, in vitro assay employing the SARS-CoV-2-Main protease inhibition assay was done to test the inhibitors’ ability to block the common primary protease of the SARS-CoV-2 virus as a mode of action. The obtained results show that the one non-linker analog 6h and two amide-based linkers 6i and 6q were the most active compounds with IC50 values of 5.08, 3.16, and 7.55 μM, respectively, against the viral protease in comparison to data of the selective antiviral agent GC-376. Molecular modeling studies were done for compound placement within the binding pocket of protease which reveal conserved residues hydrogen bonding and non-hydrogen interactions of 6i analog fragments: triazole scaffold, aryl part, and linker. Moreover, the stability of compounds and their interactions with the target pocket were also studied and analyzed by molecular dynamic simulations. The physicochemical and toxicity profiles were predicted, and the results show that compounds behave as an antiviral activity with low or no cellular or organ toxicity. All research results point to the potential usage of new chemotype potent derivatives as promising leads to be explored in vivo that might open the door to rational drug development of SARS-CoV-2 Main protease potent medicines.