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A small library of new class of dispiropyrrolidinyl-piperidone tethered indono[1,2- b ]quinoxaline heterocyclic hybrids 7 a – j were synthesized employing multicomponent 1,3-dipolar cycloaddition strategy in [bmim]Br. The azomethine ylide employed is first of its kind and generated in situ from indenoquinoxalinone and l -tryptophan, a combination that has not been employed previously for the in situ generation of azomethine ylides. The synthesized heterocyclic hybrids 7a – j were evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, therein compounds 7h and 7j displayed more potent AChE and BChE enzyme inhibition than the standard drug with IC 50 values of 3.22, 2.01, 12.40 and 10.45 mM, respectively. Molecular docking studies have also been investigated for most active compounds that disclosed interesting binding templates to the active site channel of cholinesterase enzyme. [ABSTRACT FROM AUTHOR]

Graphical abstract Highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields and assessed for their potential as inhibitors of AD. Compound bearing nitro groups on both the aryl rings showed the highest activity and this is also supported by its inhibition mechanisms on AChE and BChE receptors. Highlights • Novel highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields. • The structure of 4 H -pyrans were confirmed by FT-IR and NMR spectroscopic studies. • The compounds were evaluated as potential agents for Alzheimer's disease. • Molecular docking simulation was performed to disclose the mechanism of inhibition. Abstract Novel highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields under simple grinding at ambient temperature and were assessed for their potential for treating Alzheimer's disease (AD). The 2-amino-4 H -pyran bearing nitro groups on both the aryl rings showed the highest activity, with an IC 50 of 1.98 ± 0.09 µM against acetylcholinesterase (AChE) and 10.62 ± 0.21 µM against butyrylcholinesterase (BChE), the inhibition mechanisms on AChE and BChE receptors were revealed by means of molecular docking simulations. [ABSTRACT FROM AUTHOR]

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7- b ]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC 50 1.88 and 1.98 μM), and BChE (IC 50 18.32 and 10.21 μM) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors. [ABSTRACT FROM AUTHOR]

• Series of phenoxyimine compounds are synthesized. • Compounds were characterized by spectroscopic and analytical methods. • Cytotoxicity of synthesized compounds were performed and compounds exhibit good activity. • Docking studies were carried out to understand structure-activity relationship. • Antioxidant, cytocompatibility and haemolytic acitvities showed that compounds are nontoxic to healthy cells. A series of phenoxyimine compounds were designed and synthesized by the condensation of different substituted salicylaldehyde and aniline at the molar ratio of 1:1 in one step reaction. All synthesized compounds were characterized by analytical and spectroscopic techniques. All compounds were screened for cytotoxicity activities against different cancer cell lines. Compound 3 exhibits significant cytotoxic activity with an IC 50 value of 1.099 µM, 1.132 µM against COLO-205 (Colorectal adenocarcinoma) and A-549 (Lung carcinoma) cell line respectively, while compound 4 exhibits noteworthy cytotoxic activity with an IC 50 value of 0.52 µM against MDA-MB-231(Breast adenocarcinoma). Similarly, other compounds also exhibited good cytotoxicity properties. Furthermore, the phenoxyimine compounds showed the greatest antioxidant activity against DPPH radicals. The nontoxic activity was confirmed by cytocompatibility assay on L929 normal cell line and hemolysis assay on human red blood cells. Additionally, in silico molecular docking of all compounds were carried out against EGFR, HER-2 and VEGF. Compound 3 having minimum binding energy ΔGb = -8.81 kcal/mol, ΔGb = -10.49 kcal /mol, ΔGb = -9.99 kcal /mol, was bound into the active pocket of EGFR, HER-2 and VEGF respectively. [ABSTRACT FROM AUTHOR]

Active site of h AChE showing the docked compounds, (6f) and (6i) in the binding pocket of enzyme. A small library of structurally fascinating spiropyrrolidine tethered imidazole heterocylic hybrids has been synthesized regioselectively in good yields employing [bmim]Br mediated 1,3-diplar cycloaddition strategy. The new class of azomethine ylide generated in situ from l -histidine and 11 H -indeno[1,2- b ]quinoxalin-11-one reacts with various substituted β -nitrostyrenes affording the spiropyrrolidine tethered imidazole heterocylic hybrids. Compounds thus synthesized were assessed for their in vitro cholinesterase (ChEs) inhibitory activities, among them compounds possessing 4-methyl and 4-methoxy substituents on the aryl ring showed potent activities with IC 50 values of 2.02 ± 0.05 and 2.05 ± 0.06 μM against AChE and 12.40 ± 0.14 and 11.45 ± 0.28 μM against BChE enzyme, respectively. In addition, the most active compounds were performed for their molecular docking simulation and the results revealed interesting binding templates to the active site channel of cholinesterase enzymes. [ABSTRACT FROM AUTHOR]