Organosilicon Molecules with Medicinal Applications

Franz, Annaliese K.; Wilson, Sean O.

doi:10.1021/jm3010114

Cited by 846 publications

(383 citation statements)

References 113 publications

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“…[1][2][3][4] In recent years, various silicon-containing bioactive compounds have been reported, such as BNP1350 (1), sila-haloperidol (2) and TAC101 (3) (Fig. 1), [5][6][7] and clinical studies have supported the idea that sila-substitution can improve the selectivity, potency and pharmacokinetics of drug candidates.…”

mentioning

confidence: 97%

Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists

Kajita

Nakamura

Matsumoto

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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mentioning

confidence: 97%

Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists

Kajita

Nakamura

Matsumoto

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…2 Growing interest in the utility of (hetero)arylsilanes in synthesis, 3 medicinal chemistry 4 and materials science 5 has fuelled the development of powerful C-H silylation methods, 6,7 as exemplified by recent work on indole substrates (Figure 1). Rh-7b , Ir-8 and even t BuOKcatalysed 9 reactions have been shown to deliver C2-silylated indoles selectively, whilst C3-H silylation has been achieved using more specialised Ru complexes.…”

Section: Ru-catalysed C-h Silylation Of Unprotected Gramines Tryptammentioning

confidence: 99%

Ru-catalysed C–H silylation of unprotected gramines, tryptamines and their congeners

et al. 2016

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“…Also no well-known intrinsic "element-specific" toxicity is related to organosilicon molecules. 22 Recently, it has been reported that the C/Si exchange has lead to the identification of potent p38 allosteric inhibitors. 23 The present study was performed to understand the binding mechanism of allosteric inhibitors and p38 in DFG-out conformation, by combining molecular docking, dynamics simulation, MM-GBSA free energy calculation and per residue energy decomposition techniques.…”

Section: 18mentioning

confidence: 99%

Theoretical Characterization of Binding Mode of Organosilicon Inhibitor with p38: Docking, MD Simulation and MM/GBSA Free Energy Approach

Gadhe¹,

Balupuri²,

Kothandan³

et al. 2014

Bulletin of the Korean Chemical Society

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P38 mitogen activated protein (MAP) kinase is an important anti-inflammatory drug target, which can be activated by responding to various stimuli such as stress and immune response. Based on the conformation of the conserved DFG loop (in or out), binding inhibitors are termed as type-I and II. Type-I inhibitors are ATP competitive, whereas type-II inhibitors bind in DFG-out conformation of allosteric pocket. It remains unclear that how these allosteric inhibitors stabilize the DFG-out conformation and interact. Organosilicon compounds provide unusual opportunity to enhance potency and diversity of drug molecules due to their low toxicity. However, very few examples have been reported to utilize this property. In this regard, we performed docking of an inhibitor (BIRB) and its silicon analog (Si-BIRB) in an allosteric binding pocket of p38. Further, molecular dynamics (MD) simulations were performed to study the dynamic behavior of the simulated complexes. The difference in the biological activity and mechanism of action of the simulated inhibitors could be explained based on the molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy per residue decomposition. MM/GBSA showed that biological activities were related with calculated binding free energy of inhibitors. Analyses of the per-residue decomposed energy indicated that van der Waals and non-polar interactions were predominant in the ligand-protein interactions. Further, crucial residues identified for hydrogen bond, salt bridge and hydrophobic interactions were Tyr35, Lys53, Glu71, Leu74, Leu75, Ile84, Met109, Leu167, Asp168 and Phe169. Our results indicate that stronger hydrophobic interaction of Si-BIRB with the binding site residues could be responsible for its greater binding affinity compared with BIRB.

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Organosilicon Molecules with Medicinal Applications

Cited by 846 publications

References 113 publications

Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists

Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists

Ru-catalysed C–H silylation of unprotected gramines, tryptamines and their congeners

Theoretical Characterization of Binding Mode of Organosilicon Inhibitor with p38: Docking, MD Simulation and MM/GBSA Free Energy Approach

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