An application of two MIFs-based tools (Volsurf+ and Pentacle) to binary QSAR: The case of a palinurin-related data set of non-ATP competitive Glycogen Synthase Kinase 3β (GSK-3β) inhibitors

Ermondi, Giuseppe; Caron, Giulia; Pintos, Isela García; Gerbaldo, M.; Pérez, Manuel; Pérez, Daniel I.; Gándara, Zoila; Martı́nez, Ana; Gómez, Generosa; Fall, Yagamare

doi:10.1016/j.ejmech.2010.12.024

Cited by 23 publications

(13 citation statements)

References 25 publications

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“…Total synthesis of palinurin has been recently described providing a new source for this lead compound (Perez et al, 2009b). Different studies have been performed to determine structure activity relationships among a series of congeneric molecules and the bioactive conformation has been proposed (Ermondi et al, 2011). However, the binding mode to GSK-3 remains unknown.…”

Section: Organic Molecules As Gsk-3 Inhibitorsmentioning

confidence: 99%

GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS

Eldar-Finkelman

Martı́nez

2011

Front. Mol. Neurosci.

303

278

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Inhibiting glycogen synthase kinase-3 (GSK-3) activity via pharmacological intervention has become an important strategy for treating neurodegenerative and psychiatric disorders. The known GSK-3 inhibitors are of diverse chemotypes and mechanisms of action and include compounds isolated from natural sources, cations, synthetic small-molecule ATP-competitive inhibitors, non-ATP-competitive inhibitors, and substrate–competitive inhibitors. Here we describe the variety of GSK-3 inhibitors with a specific emphasis on their biological activities in neurons and neurological disorders. We further highlight our current progress in the development of non-ATP-competitive inhibitors of GSK-3. The available data raise the hope that one or more of these drug design approaches will prove successful at stabilizing or even reversing the aberrant neuropathology and cognitive deficits of certain central nervous system disorders.

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Section: Organic Molecules As Gsk-3 Inhibitorsmentioning

confidence: 99%

GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS

Eldar-Finkelman

Martı́nez

2011

Front. Mol. Neurosci.

303

278

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“…Many studies have been realized for search of new GSK-3β inhibitors by applying LBDD [39,[61][62][63][64][65][66][67][68][69][70]. The most promising work in this area is related with the first computational chemistry mt-QSAR model for anti-AD, antiparasitic, anti-fungi, and anti-bacterial activity of GSK-3 inhibitors [39].…”

Section: Glycogen Synthase Kinase-3β (Gsk-3β)mentioning

confidence: 98%

Role of Ligand-Based Drug Design Methodologies toward the Discovery of New Anti- Alzheimer Agents: Futures Perspectives in Fragment-Based Ligand Design

Speck‐Planche

Luan²,

Cordeiro³

2012

CMC

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Alzheimer's disease (AD), a degenerative disease affecting the brain, is the single most common source of dementia in adults. The cause and the progression of AD still remains a mystery among medical experts. As a result, a cure has not yet been discovered, even after decade's worth of research that started since 1906, when the disease was first identified. Despite the efforts of the scientific community, several of the biological receptors associated with AD have not been sufficiently studied to date, limiting in turn the design of new and more potent anti-AD agents. Thus, the search for new drug candidates as inhibitors of different targets associated with AD constitutes an essential part towards the discovery of new and more efficient anti-AD therapies. The present work is focused on the role of the Ligand-Based Drug Design (LBDD) methodologies which have been applied for the elucidation of new molecular entities with high inhibitory activity against targets related with AD. Particular emphasis is given also to the current state of fragment-based ligand approaches as alternatives of the Fragment-Based Drug Discovery (FBDD) methodologies. Finally, several guidelines are offered to show how the use of fragment-based descriptors can be determinant for the design of multi-target inhibitors of proteins associated with AD.

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“…We built models with the four sets and selected the model with the best statistical performance (AMANDA/CLACC for both models). Since the L-VDCC inhibition percentage at 1 M reported in the original paper [6] is not an appropriate biological endpoint because of the nonlinear characteristic of dose/response relationships, for the calcium channel blocking model we decided to adopt a simple binary classification of data [18]. Compounds with the L-VDCC inhibition percentage larger than 80%…”

Section: Molecular Modelingmentioning

confidence: 99%

“…and O probes that mimic respectively water, hydrophobic, hydrogen bond acceptor and hydrogen bond donor interaction of the compounds with the environment) [18,20]. The molecules were projected on the pre-calculated models implemented in VolSurf+ to calculate ADME-Tox parameters and solubility.…”

Section: Molecular Modelingmentioning

confidence: 99%