A combined in vitro , in silico and Polyphenolic Profile of stem extracts of Juncus maritimus (Juncaceae) harvested from eastern Algeria as potential anti-inflammatory and antioxidant agents.

The extremophilic species Juncus maritimus known for its medicinal virtues was collected in the Biskra region with the aim of its valorization. The volume size of polyphenols, flavonoids and condensed tannins was carried out by Folin-Ciocalteu methods, aluminum trichloride and vanillin respectively. Polyphenols volume is 127.73±0.20 µg EAG/mg ES, flavonoids 16.42±0.42 µg EQ/mg ES and condensed tannins 10.10±0.35 µg EC/mg ES. The result of antioxidant activity tested by employing DPPH and ABTS methods reveal that the ethyl acetate extract had the highest activity in both tests. The result of in vitro anti-inflammatory activity, by the BSA protein denaturation test, showed that the percentage inhibition of denaturation is proportional to the concentration of the extract. At a concentration of 5 mg/mL, the percentage inhibition of the extract was close to that an anti-inflammatory drug Diclofenac with 82.03 and 80.23% respectively. Furthermore, molecular docking simulations revealed that Berberine was shown high binding affinity with the COX-2 and PLA-2 targets. Indeed, bioisosteric replacement is applied to discover novel analogs of Berberine. Finally, ADME-Tox prediction demonstrated that this compound and its analogs are without Hepatotoxicity. The results might be selecting that Berberine and its analogs as active compound with anti-inflammatory and antioxidant activities.

Molecular docking/dynamics simulations, MEP analysis, bioisosteric replacement and ADME/T prediction for identification of dual targets inhibitors of Parkinson's disease with novel scaffold.

Monoamine oxidase B and Adenosine A2A receptors are used as key targets for Parkinson's disease. Recently, hMAO-B and hA2AR Dual-targets inhibitory potential of a novel series of Phenylxanthine derivatives has been established in experimental findings. Hence, the current study examines the interactions between 38 compounds of this series with hMAO-B and hA2AR targets using different molecular modeling techniques to investigate the binding mode and stability of the formed complexes. A molecular docking study revealed that the compounds L24 ((E)-3-(3-Chlorophenyl)-N-(4-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl) phenyl) acrylamide and L32 ((E)-3-(3-Chlorophenyl)-N-(3-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)phenyl)acrylamide) had a high affinity (S-score: -10.160 and -7.344 kcal/mol) with the pocket of hMAO-B and hA2AR targets respectively, and the stability of the studied complexes was confirmed during MD simulations. Also, the MEP maps of compounds 24 and 32 were used to identify the nucleophilic and electrophilic attack regions. Moreover, the bioisosteric replacement approach was successfully applied to design two new analogs of each compound with similar biological activities and low energy scores. Furthermore, ADME-T and Drug-likeness results revealed the promising pharmacokinetic properties and oral bioavailability of these compounds. Thus, compounds L24, L32, and their analogs can undergo further analysis and optimization in order to design new lead compounds with higher efficacy toward Parkinson's disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00139-3.