Design and synthesis of 4-arylpiperidinyl amide and N-arylpiperdin-3-yl-cyclopropane carboxamide derivatives as novel melatonin receptor ligands

Li, Guiying; Zhou, Hao; Yu, Jinhui; Keim, H.; Topiol, Sidney W.; Poda, Suresh B.; Ren, Yang; Chandrasena, Gamini; Doller, Darı́o

doi:10.1016/j.bmcl.2010.12.068

Cited by 17 publications

(15 citation statements)

References 27 publications

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“…Dogsite web server was employed to detect the binding pocket of ASMT (Table 1) [25]. Seventy three structurally diverse ASMT inhibitors (Additional file 1) with representative good biological activity were selected from the literature [26-31]. The 2D structures of the melatoninergic inhibitors were drawn using chemical structure drawing package, ChemOffice 2004 [32].…”

Section: Methodsmentioning

confidence: 99%

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines

Azam

Abbasi

2013

Theor Biol Med Model

183

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BackgroundN-Acetylserotonin O-methyltransferase (ASMT) is an enzyme which by converting nor-melatonin to melatonin catalyzes the final reaction in melatonin biosynthesis in tryptophan metabolism pathway. High Expression of ASMT gene is evident in PPTs. The presence of abnormally high levels of ASMT in pineal gland could serve as an indication of the existence of pineal parenchymal tumors (PPTs) in the brain (J Neuropathol Exp Neurol 65: 675–684, 2006). Different levels of melatonin are used as a trait marker for prescribing the mood disorders e.g. Seasonal affective disorder, bipolar disorder, or major depressive disorder. In addition, melatonin levels can also be used to calculate the severity of a patient’s illness at a given point in time.MethodsSeventy three melatoninergic inhibitors were docked with acetylserotonin-O-methyltransferase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking routines. Keeping this fact in view, critical evaluation of the performance of four different commonly used docking routines: AutoDock/Vina, GOLD, FlexX and FRED were performed. An evaluation criterion was based on the binding affinities/docking scores and experimental bioactivities.Results and conclusionResults indicated that both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and the compound selected as potent inhibitor is having minimum binding affinity, maximum GoldScore and minimum FlexX energy. The correlation value of r2 = 0. 66 may be useful in the selection of correct docked complexes based on the energy without having prior knowledge of the active site. This may lead to further understanding of structures, their reliability and Biomolecular activity especially in connection with bipolar disorders.

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Section: Methodsmentioning

confidence: 99%

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines

Azam

Abbasi

2013

Theor Biol Med Model

183

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“…Li and co-workers successfully coupled another amide-substituted piperidine ( 62 ) to access melatonin receptor ligand 63 , employed in a study of sleep disorders ( Scheme 10 c). 84 …”

Section: Alkylaminesmentioning

confidence: 99%

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

2016

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Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

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“…(3) Ligand-Protein Docking . For predicting the binding affinities of a variety of ligands, molecular docking protocols are commonly used [ 39 ]. The parameters of molecular docking software were used to conduct the experiments ( https://www.ccdc.cam.ac.uk/ ).…”

Section: Methodsmentioning

confidence: 99%

Integrating In Silico and In Vitro Approaches to Screen the Antidiabetic Properties from Tabernaemontana divaricata (Jasmine) Flowers

Muzammil

Andleeb

Hayat

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The purpose of this study was to assess different in vitro biological activities such as phytochemical constituents, enzymatic antioxidant status, cytotoxicity through hemolytic activity, and antidiabetic potential of plant methanolic extract through glucose uptake by yeast cells. Further, using in silico approach by the SwissADME technique the drug-likeness rules for bioactive components were characterized, while potential interactions were identified via molecular docking of a ligand with target proteins by GOLD 5.3.0. The results showed that T. divaricata was rich in TPC and TFC, i.e., 62.32 ± 4.02 and 24.53 ± 0.61, respectively, and the cytotoxic potential was 10% towards human RBCs, while protein estimation revealed the presence of protein in the extract, which was 22.82 ± 4.6. DPPH assay in comparison with ascorbic acid and several enzymatic assays, such as CAT, SOD, and POD, showed maximum antioxidant potential, i.e.,15.9 ± 2.33%, 65.57 ± 13.4%, 3.02 ± 3.4, 15.87 ± 0.5, and 0.74 ± 0.2, respectively. Glucose uptake by yeast cells, i.e., α-amylase and α-glucosidase, showed a maximum antidiabetic potential such as 75.11 ± 1.44%, 41.81 ± 3.75%, and 35.9 ± 1.24%, respectively. Our results indicate that the methanolic extract of T. divaricata has antioxidant potential and inhibits α-amylase and α-glucosidase activity and possesses maximum antidiabetic potential. The results provide scientific proof that the medicinal plant being studied is a powerful source of natural antioxidant, antidiabetic, and medicinally significant substances. In silico study, using a molecular docking, unveiled that two compounds showed good interactions with 5kzw protein with considerable binding affinities and fulfilled docking parameters. It may conclude that T. divaricata is an important vegetable with a potent source of natural antioxidants and antidiabetic activity justifying its traditional use in green therapeutics.

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Design and synthesis of 4-arylpiperidinyl amide and N-arylpiperdin-3-yl-cyclopropane carboxamide derivatives as novel melatonin receptor ligands

Cited by 17 publications

References 27 publications

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Integrating In Silico and In Vitro Approaches to Screen the Antidiabetic Properties from Tabernaemontana divaricata (Jasmine) Flowers

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