Prostrate knotweed also called Polygonum aviculare is an important edible plant. The polygonum is majorly known for the phenolics and antioxidants. The antioxidants combat the excessive free radicals within the body. The excessive free radicals are implicated in various other diseases like diabetes, Alzheimer’s, and inflammation. This study was aimed at exploring the antioxidant bioactives and their derivatizations to produce new molecules with advanced pharmacological features. We have isolated six compounds (1–6) from Polygonum aviculare. Furthermore, rational‐based chemical derivatives for compound 5 have been formed for the management of diabetes, Alzheimer’s, and inflammation. In preliminary antioxidant studies, all the isolated compounds (1–6) showed potential results against DPPH and ABTS free radicals. Based on the IC₅₀ and chemical nature of the compounds, compound 5 was subjected to derivatization. Keeping the phenolic part of compound 5 unaffected, hydroxy succinimide (5A) and thiazolidinedione (5B) were synthesized. The compound 5A was found to be a potent inhibitor of AChE, BChE, COX‐1, COX‐2, 5‐LOX, and DPPH giving IC₅₀ values of 10.60, 15.10, 13.91, 1.08, 0.71, and 1.05 μM, respectively. The COX‐2 selectivity of compound 5A was found at 12.9. The compound 5B was found to be a potent multitarget antidiabetic agent giving IC₅₀ values of 15.34, 21.83, 53.28, and 1.94 μM against α‐glucosidase, α‐amylase, protein tyrosine phosphatase 1B, and DPPH. Docking studies were performed to manipulate the binding interactions. The docking pose of all the tested compounds was found to have increased binding affinity against all tested targets that supported the in vitro results. Our results showed that Polygonum aviculare is a rich source of antioxidant compounds. The two new derivatives have enhanced pharmacological features to treat diabetes, inflammation, and Alzheimer’s disease.

Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E₂, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable ( ) till the 5th hour of test sample injection. Compound D also exhibited excellent percent inhibition (63.81 ± 2.24%) at the highest dose in arachidonic acid-induced ear inflammation. On the basis of in vivo and in vitro results, compound D was subjected to various inflammation-causing agents such as histamine, prostaglandins E₂, bradykinin, and leukotriene via the mouse paw edema test. Compound D revealed moderate effect (28.10 ± 1.64%) against histamine-induced paw edema while nonsignificant result (9.72 ± 3.125%) was marked for the bradykinin pathway. Compound D showed significance against edematogenic consequence of prostaglandin E₂ (56.28–72.03%) and leukotriene (55.13 ± 2.25%) induced inflammation. In summary, our findings recommended that compound D possesses double acting anti-inflammatory properties inhibiting both COX and LOX pathways. Binding orientations and energy values computed via docking simulations support the results of the experimental in vitro evaluation.

Background: Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-β-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition. Methods: The compounds (4, 9– 11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target. Results: Four Michael adducts (4, 9– 11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC₅₀ values of 128 and 65 μM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC₅₀ value of 5.79 μM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions. Conclusion: Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.

Electrochemical energy storage devices are ubiquitous for personal electronics, electric vehicles, smart grids, and future clean energy demand. SCs are EES devices with excellent power density and superior cycling ability. Herein, we focused on the fabrication and DFT calculations of Na₃-δ-MnO₂ nanocomposite, which has layered MnO₂ redox-active sites, supported on carbon cloth. MnO₂ has two-dimensional diffusion channels and is not labile to structural changes during intercalation; therefore, it is considered the best substrate for intercalation. Cation pre-intercalation has proven to be an effective way of increasing inter-layered spacing, optimizing the crystal structure, and improving the relevant electrochemical behavior of asymmetric aqueous supercapacitors. We successfully established Na⁺ pre-intercalated δ-MnO₂ nanosheets on carbon cloth via one-pot hydrothermal synthesis. As a cathode, our prepared material exhibited an extended potential window of 0–1.4 V with a remarkable specific capacitance of 546 F g⁻¹(300 F g⁻¹ at 50 A g⁻¹). Moreover, when this cathode was accompanied by an N-AC anode in an asymmetric aqueous supercapacitor, it illustrated exceptional performance (64 Wh kg⁻¹ at a power density of 1225 W kg⁻¹) and incomparable potential window of 2.4 V and 83% capacitance retention over 10,000 cycles with a great Columbic efficiency.

In this study, a simple in situ technique followed by hydrothermal method is used to synthesize a novel tremella-like structure of ZIF-67Co(OH)F@Co₃O₄/CC metal–organic framework (MOF) derived from zeolite imidazole.