Journal ArticleDOI
Exploring 2D-QSAR for prediction of beta-secretase 1 (BACE1) inhibitory activity against Alzheimer’s disease
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TLDR
A robust quantitative structure–activity relationship (QSAR) model employing a dataset of 98 heterocycle compounds to identify structural features responsible for BACE1 (beta-secretase 1) enzyme inhibition is developed and it is concluded that heteroatoms present within to an aromatic nucleus and the structural features such as hydrophobic, ring aromatic and hydrogen bond acceptor/donor are responsible for the enhancement of the Bace1 enzyme inhibitory activity.Abstract:
We have developed a robust quantitative structure-activity relationship (QSAR) model employing a dataset of 98 heterocycle compounds to identify structural features responsible for BACE1 (beta-secretase 1) enzyme inhibition. We have used only 2D descriptors for model development purpose thus avoiding the conformational complications arising due to 3D geometry considerations. Following the strict Organization for Economic Co-operation and Development (OECD) guidelines, we have developed models using stepwise regression analysis followed by the best subset selection, while the final model was developed by partial least squares regression technique. The model was validated using various internationally accepted stringent validation parameters. From the insights obtained from the developed model, we have concluded that heteroatoms (nitrogen, oxygen, etc.) present within to an aromatic nucleus and the structural features such as hydrophobic, ring aromatic and hydrogen bond acceptor/donor are responsible for the enhancement of the BACE1 enzyme inhibitory activity. Moreover, we have performed the pharmacophore modelling to unveil the structural requirements for the inhibitory activity against the BACE1 enzyme. Furthermore, molecular docking studies were carried out to understand the molecular interactions involved in binding, and the results are then correlated with the requisite structural features obtained from the QSAR and pharmacophore models.read more
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Exploring QSAR models for assessment of acute fish toxicity of environmental transformation products of pesticides (ETPPs).
TL;DR: From the developed model, lipophilicity, polarity, presence of branching and the functional form of O-atom in the transformed structures of pesticides are the important features that are to be considered during ecotoxicity assessment of ETPPs.
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In silico modeling for dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes in Alzheimer's disease.
TL;DR: The features obtained from the 2D-QSAR modeling suggest that the number of aromatic ethers, unsaturation content relative to the molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comparison to the BuChE enzymes.
Journal ArticleDOI
Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer's Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches.
Oluwafemi Adeleke Ojo,Adebola Busola Ojo,Charles E. Okolie,Mary-Ann Chinyere Nwakama,Matthew Iyobhebhe,Ikponmwosa Owen Evbuomwan,Charles Obiora Nwonuma,Rotdelmwa Filibus Maimako,Abayomi Emmanuel Adegboyega,Odunayo Anthonia Taiwo,Khalaf F. Alsharif,Gaber El-Saber Batiha +11 more
TL;DR: In this article, the authors evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholine-choline (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies.
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Design of Curcumin and Flavonoid Derivatives with Acetylcholinesterase and Beta-Secretase Inhibitory Activities Using in Silico Approaches.
TL;DR: The study indicated that, by using in silico methods, a series of curcumin and flavonoid structures were generated with promising predicted bioactivities, which could be potential candidates for further research and lead optimization.
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Amalgamation of in-silico, in-vitro and in-vivo approach to establish glabridin as a potential CYP2E1 inhibitor.
S. B. Bhatt,S. B. Bhatt,Vinay Kumar,Ashish Dogra,Ashish Dogra,Probir Kumar Ojha,Priya Wazir,Payare L. Sangwan,Payare L. Sangwan,Gurdarshan Singh,Gurdarshan Singh,Utpal Nandi,Utpal Nandi +12 more
TL;DR: In this paper, the authors identified a potential CYP2E1 inhibitor from experimental bio-flavonoids which are unexplored for CYP 2E1 inhibition till date using in-silico, in-vitro and invivo approaches.
References
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Journal ArticleDOI
Triazolyl tryptoline derivatives as β-secretase inhibitors
TL;DR: Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against Bace1 was used as a scaffold for the design of BACE1 inhibitors.
Journal ArticleDOI
Synthesis of Tetramic and Tetronic Acids as β-Secretase Inhibitors
Gregor Larbig and,Boris Schmidt +1 more
TL;DR: The activities of tetronic and tetramic acids on BACE-1 inhibition are reported, which feature a low molecular weight and compact scaffold, which is accessible by solid-phase-supported diverse synthesis.
Journal ArticleDOI
Multilayered Variable Selection in QSPR: A Case Study of Modeling Melting Point of Bromide Ionic Liquids
TL;DR: In this paper, the authors developed predictive quantitative structure-property relationship (QSPR) models for melting point of bromide Ionic liquids (ILs) and used a multilayered variable selection strategy for development of final QSPR models.
Journal ArticleDOI
Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease.
Nalini Schaduangrat,Veda Prachayasittikul,Saowapak Choomwattana,Prapimpun Wongchitrat,Kamonrat Phopin,Wilasinee Suwanjang,Aijaz Ahmad Malik,Bruno Vincent,Bruno Vincent,Chanin Nantasenamat +9 more
TL;DR: This review article attempts to comprehensively cover aspects related to the identification and use of drugs targeting the secretase enzymes, a group of proteases responsible for the metabolism of the β‐amyloid precursor protein (βAPP) and β‐AMyloid peptides production, and their therapeutic modulation.
Journal ArticleDOI
The discovery of novel β-secretase inhibitors: pharmacophore modeling, virtual screening, and docking studies.
Yan Niu,Chao Ma,Hongwei Jin,Fengrong Xu,Haifei Gao,Peng Liu,Yongjian Li,Chao Wang,Guanyu Yang,Ping Xu +9 more
TL;DR: The identification of two small molecular inhibitors for β‐secretase by integrating virtual screening with fluorescence resonance energy transfer bioassay and molecular docking could represent new potentials for the development of anti‐Alzheimer’s disease agents.
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