The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Arup Mukherjee - One of the best experts on this subject based on the ideXlab platform.
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exploring molecular Structural Requirement for ache inhibition through multi chemometric and dynamics simulation analyses
Journal of Biomolecular Structure & Dynamics, 2018Co-Authors: Tabassum Hossain, Achintya Saha, Arup MukherjeeAbstract:The acetylcholinesterase enzyme (AChE) plays an important role in central and peripheral nervous systems. Acetylcholine (ACh) acts through the regulation of AChE activity, which can play a key role in accelerating senile amyloid β-peptide (Aβ) plaque deposition. Therefore, inhibition of the AChE enzyme can be used as a key principle to prevent ACh depletion. The present study has been emphasized to explore both ligand- and structure-based 3D QSAR, HQSAR, pharmacophore, molecular docking and simulation studies on a set of Structurally diverse inhibitors to optimize prime Structural features responsible for selective binding to AChE, and vis-a-vis inhibiting enzyme activity. The pharmacophore model showed the importance of HB acceptor and donor, positive ionization and hydrophobic features of the molecule for effective binding. Structure-based docking and simulation studies adjudged the significance of features obtained from ligand-based 3D QSAR, CoMFA (Q2 = .608, = .700), CoMSIA (Q2 = .632, = .734), HQSA...
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molecular modeling studies on Structural Requirement of diarylpropionitrile for selectivity to estrogen receptor subtypes
Medicinal Chemistry Research, 2012Co-Authors: Ataul Islam, Ria Pal, Tabassum Hossain, Arup Mukherjee, Achintya SahaAbstract:Molecular modeling techniques are widely used to discover drug candidates for selective disease. In the present study, ligand-based drug design techniques have been explored to find the Structural Requirement of diarylpropionitrile derivatives, a group of non-steroidal estrogen receptor (ER) modulators for selective binding to receptor subtypes. 2D/3D quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies have been explored for this purpose. The classical QSAR models (Rα2 = 0.870, Qα2 = 0.813, Rα-pred2 = 0.636; Rβ2 = 0.853, Qβ2 = 0.745, Rβ-pred2 = 0.565) show the importance of molecular refractivity, electronic contribution of atoms C3, C7, C13 and C14, and R2 and R4 substituents (Fig. 1) for specificity. The 3D QSAR, molecular fields (CoMFA, Rα2 = 0.999, Qα2 = 0.679, Rα-pred2 = 0.678 and Rβ2 = 0.999, Qβ2 = 0.611, Rβ-pred2 = 0.691) and similarity (CoMSIA, Rα2 = 0.999, Qα2 = 0.670, Rα-pred2 = 0.686 and Rβ2 = 0.999, Qβ2 = 0.671, Rβ-pred2 = 0.590) analyses show contour maps of steric, hydrophobic along with hydrogen bond (HB) donor and acceptor are important factors for binding affinity to both α- and β-subtypes. In addition, electronic contribution is crucial for α-subtype binding. Pharmacophore models derive the importance of HB acceptor and donor, aromatic ring, molecular steric, and hydrophobic interactions for selective binding to receptor subtypes. The derived models are correlated with structure-based molecular docking study, explaining the significant interactions between receptor and ligand for selective subtypes binding. Open image in new window Fig. 1 General structure of diarylpropionitrile scaffold. Common atoms are numbered through 1–14
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Molecular modeling studies on Structural Requirement of diarylpropionitrile for selectivity to estrogen receptor subtypes
Medicinal Chemistry Research, 2012Co-Authors: Md Ataul Islam, Ria Pal, Tabassum Hossain, Arup Mukherjee, Achintya SahaAbstract:Molecular modeling techniques are widely used to discover drug candidates for selective disease. In the present study, ligand-based drug design techniques have been explored to find the Structural Requirement of diarylpropionitrile derivatives, a group of non-steroidal estrogen receptor (ER) modulators for selective binding to receptor subtypes. 2D/3D quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies have been explored for this purpose. The classical QSAR models ( R _α ^2 = 0.870, Q _α ^2 = 0.813, R _α-pred ^2 = 0.636; R _β ^2 = 0.853, Q _β ^2 = 0.745, R _β-pred ^2 = 0.565) show the importance of molecular refractivity, electronic contribution of atoms C_3, C_7, C_13 and C_14, and R_2 and R_4 substituents (Fig. 1 ) for specificity. The 3D QSAR, molecular fields (CoMFA, R _α ^2 = 0.999, Q _α ^2 = 0.679, R _α-pred ^2 = 0.678 and R _β ^2 = 0.999, Q _β ^2 = 0.611, R _β-pred ^2 = 0.691) and similarity (CoMSIA, R _α ^2 = 0.999, Q _α ^2 = 0.670, R _α-pred ^2 = 0.686 and R _β ^2 = 0.999, Q _β ^2 = 0.671, R _β-pred ^2 = 0.590) analyses show contour maps of steric, hydrophobic along with hydrogen bond (HB) donor and acceptor are important factors for binding affinity to both α- and β-subtypes. In addition, electronic contribution is crucial for α-subtype binding. Pharmacophore models derive the importance of HB acceptor and donor, aromatic ring, molecular steric, and hydrophobic interactions for selective binding to receptor subtypes. The derived models are correlated with structure-based molecular docking study, explaining the significant interactions between receptor and ligand for selective subtypes binding. Fig. 1 General structure of diarylpropionitrile scaffold. Common atoms are numbered through 1–14
Sang-hun Jung - One of the best experts on this subject based on the ideXlab platform.
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Structural Requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase.
Bioorganic & medicinal chemistry letters, 2011Co-Authors: Pillaiyar Thanigaimalai, Ki-cheul Lee, Vinay K. Sharma, Cheonik Joo, Won-jea Cho, Eunmiri Roh, Youngsoo Kim, Sang-hun JungAbstract:Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3-alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N'-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor.
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Structural Requirement s of n phenylthioureas and benzaldehyde thiosemicarbazones as inhibitors of melanogenesis in melanoma b 16 cells
Bioorganic & Medicinal Chemistry Letters, 2010Co-Authors: Pillaiyar Thanigaimalai, Ki-cheul Lee, Vinay K. Sharma, Eunmiri Roh, Youngsoo Kim, Seong-cheol Bang, Tuan Anh Le Hoang, Cheong Yong Yun, Bang Yeon Hwang, Sang-hun JungAbstract:Abstract In order to define the Structural Requirements of phenylthiourea (PTU), a series of thiourea and thiosemicarbazone analogs were prepared and evaluated as inhibitors of melanogenesis in melanoma B16 cells. The most potent analog was 2-(4- tert -butylbenzylidene)hydrazinecarbothioamide (1u) with an IC 50 value of 2.7 μM in inhibition of melanogenesis. The structure for potent inhibitory activity of these derivatives are required with the direct connection of π-planar structure to thiourea without steric hinderance in PTU derivatives and the hydrophobic substituent at para position in case of semicarbazones.
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Structural Requirement of isoflavonones for the inhibitory activity of interleukin 5
European Journal of Medicinal Chemistry, 2003Co-Authors: Sang-hun Jung, Soohyun Cho, Jee Hyun Lee, Mikyung Kim, Seungho Lee, Jaechun Ryu, Youngsoo KimAbstract:Abstract Sophoricoside isolated from Sophora japonica is a glycoside of isoflavonone as an inhibitor of interleukin (IL)-5. To identify Structural Requirements of this isoflavonone for its inhibitory activity against IL-5, isoflavonones, isoflavanones, and their glycosides were prepared and their inhibitory activity was tested against IL-5. Among them, 5-benzyloxy-3-(4-hydroxyphenyl)chromen-4-one ( 4b , 87.9% inhibition at 50 μM, IC 50 =15.3 μM) shows the most potent activity, comparable with that of sophoricoside. The important Structural Requirements of these isoflavonone analogs exhibiting the inhibitory activity against IL-5 were recognized as (1) planarity of chromen-4-one ring, (2) existence of phenolic hydroxyl at 4-position of B ring, and (3) introduction of benzyloxy at 5-position, which may act as a bulky group for occupying hydrophobic pocket in putative binding site. However the glucopyranosyl moiety of sophoricoside is not an essential motif for the activity.
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planar Structural Requirement at 4 position of 1 arylsulfonyl 4 phenyl 4 5 dihydro 2 imidazolones for their cytotoxicity
Archives of Pharmacal Research, 1997Co-Authors: Sang-hun Jung, Suhkjun KwakAbstract:In order to identify the Structural Requirement at 4-position of 1-arylsulfonyl-4-phenyl-4,5-dihydro-2-limidazolones3 for their cytotoxicity, the corresponding 1-arylsulfonyl-4-cyclohexyl-4,5-dihydro-2-imidazolones4 were synthesized and theirin vitro cytotoxicity against human solid tumor cell lines were measured. Unlike compounds3a-c, cyclohexyl analogues4a-c do not show the cytotoxicity. This dramatic loss of activity of these analogues on the volume change with the bulkier cyclohexyl group indicates that the planar structure at 4-position of 1-arylsulfonyl-4-phenyl-4,5-dihydro-2-limidazolones3 is required for their activity as an important pharmacophoric moiety.
Hiroshi Saito - One of the best experts on this subject based on the ideXlab platform.
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Structural Requirement for axonal regeneration promoting effect of polyamines in cultured rat hippocampal neurons
Brain Research, 1997Co-Authors: Kazuho Abe, Peng-jiang Chu, Akira Shirahata, Keijiro Samejima, Hiroshi SaitoAbstract:Abstract We have previously found that spermine, spermidine and putrescine promote axonal regeneration following axotomy in cultured rat hippocampal neurons. In the present study, we investigated which part of the polyamine molecule is responsible for the regeneration-promoting effect. Testing the effects of several synthetic analogues revealed that the butanediamine moiety is essential for the activity and the terminal primary amines are necessary for full agonist activity. The structure–activity relationship indicates that the regeneration-promoting effects of polyamines are not associated with NMDA receptors.
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Structural Requirement for neurotrophic activity of spermine in cultured rat hippocampal neurons
Japanese journal of pharmacology, 1995Co-Authors: Peng-jiang Chu, Akira Shirahata, Keijiro Samejima, Hiroshi Saito, Kazuho AbeAbstract:We investigated the structure-activity relationship for the neurotrophic activity of spermine by comparing the effects of several synthetic spermine analogues on the survival of cultured rat hippocampal neurons. N, N'' -bis(3-aminopropyl)-1, 6-hexanediamine and N, N'' -bis(3-aminopropyl)-1, 3-propanediamine did not promote the neuronal survival, suggesting that the central butanediamine structure is essential for the neurotrophic activity. Furthermore, N1, N12-bis(ethyl)spermine significantly promoted the neuron survival, but its maximum effect was smaller than that of spermine, indicating that two terminal primary amines are required for full agonist activity. The Structural Requirement for the neurotrophic activity of spermine was different from those for any other reported activities of polyamines.
Achintya Saha - One of the best experts on this subject based on the ideXlab platform.
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exploring molecular Structural Requirement for ache inhibition through multi chemometric and dynamics simulation analyses
Journal of Biomolecular Structure & Dynamics, 2018Co-Authors: Tabassum Hossain, Achintya Saha, Arup MukherjeeAbstract:The acetylcholinesterase enzyme (AChE) plays an important role in central and peripheral nervous systems. Acetylcholine (ACh) acts through the regulation of AChE activity, which can play a key role in accelerating senile amyloid β-peptide (Aβ) plaque deposition. Therefore, inhibition of the AChE enzyme can be used as a key principle to prevent ACh depletion. The present study has been emphasized to explore both ligand- and structure-based 3D QSAR, HQSAR, pharmacophore, molecular docking and simulation studies on a set of Structurally diverse inhibitors to optimize prime Structural features responsible for selective binding to AChE, and vis-a-vis inhibiting enzyme activity. The pharmacophore model showed the importance of HB acceptor and donor, positive ionization and hydrophobic features of the molecule for effective binding. Structure-based docking and simulation studies adjudged the significance of features obtained from ligand-based 3D QSAR, CoMFA (Q2 = .608, = .700), CoMSIA (Q2 = .632, = .734), HQSA...
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Exploring Structural Requirement, pharmacophore modeling, and de novo design of LRRK2 inhibitors using homology modeling approach
Medicinal Chemistry Research, 2014Co-Authors: Sagar S. Bhayye, Kunal Roy, Achintya SahaAbstract:A mutation in the gene, encoding leucine rich repeat kinase 2 (LRRK2), is a genetic cause of Parkinson’s disease (PD). LRRK2 is a dimeric multidomain protein, largely regulates guanosine triphosphate (GTP). G2019S and I2020T, the mutation encodes in the kinase domain of LRRK2 increase the GTPase activity, are the important regulators in pathogenesis of PD. To design potent LRRK2 inhibitors, pharmacophore modeling approach was employed with a wide chemical diversity of compound’s database. The best hypothesis consists of hydrogen-bond acceptor and donor as well as hydrophobic aliphatic and ring aromatic features. The model was validated by the test and decoy sets followed by Fischer’s randomization test. The validated model was used to screen the database of compounds, which were designed through de novo approach. Homology model of the kinase domain of LRRK2 was built initially using the crystal structure of Janus kinase 3. The designed molecules were further screened for ADMET properties, and ligand–receptor interaction of top hits was analyzed by molecular docking studies to explore potent LRRK2 inhibitors.
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exploring Structural Requirement and binding interactions of β amyloid cleavage enzyme inhibitors using molecular modeling techniques
Medicinal Chemistry Research, 2013Co-Authors: Tabassum Hossain, Ataul Islam, Ria Pal, Achintya SahaAbstract:β-Amyloid precursor protein cleavage enzyme (BACE) has been shown to be an attractive therapeutic target to control Alzheimer’s disease (AD). Inhibition of β-secretase enzyme can prevent the deposition of Aβ (β-amyloid) peptides, which is thought to be the major cause of AD. The present study has been considered to explore 3D-QSAR, HQSAR, and pharmacophore mapping studies of BACE inhibitors. Contour maps of 3D-QSAR studies (CoMFA: R2 = 0.998, se = 0.067, Q2 = 0.765, Rpred2 = 0.772, rm2 = 0.739; CoMSIA: R2 = 0.992, se = 0.125, Q2 = 0.730, Rpred2 = 0.713, rm2 = 0.687) explain the importance of steric and electrostatic, along with hydrogen-bond (HB) acceptor and donor for binding affinity to BACE. HQSAR study (R2 = 0.941, se = 0.326, Q2 = 0.792, Rpred2 = 0.713, rm2 = 0.709) indicates the important fragments of the molecular fingerprints that might be crucial for binding affinity. Pharmacophore space modeling (R2 = 0.937, rmsd = 0.937, Q2 = 0.935, Rpred2 = 0.709, rm2 = 0.837) describes that HB acceptor, donor, hydrophobic, and steric are the important features for interaction with receptor cavity. Finally, the models are adjudged through the docking study elucidating the interactions between the receptor and the ligand, indicating the Structural Requirements of potent BACE inhibitors.
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molecular modeling studies on Structural Requirement of diarylpropionitrile for selectivity to estrogen receptor subtypes
Medicinal Chemistry Research, 2012Co-Authors: Ataul Islam, Ria Pal, Tabassum Hossain, Arup Mukherjee, Achintya SahaAbstract:Molecular modeling techniques are widely used to discover drug candidates for selective disease. In the present study, ligand-based drug design techniques have been explored to find the Structural Requirement of diarylpropionitrile derivatives, a group of non-steroidal estrogen receptor (ER) modulators for selective binding to receptor subtypes. 2D/3D quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies have been explored for this purpose. The classical QSAR models (Rα2 = 0.870, Qα2 = 0.813, Rα-pred2 = 0.636; Rβ2 = 0.853, Qβ2 = 0.745, Rβ-pred2 = 0.565) show the importance of molecular refractivity, electronic contribution of atoms C3, C7, C13 and C14, and R2 and R4 substituents (Fig. 1) for specificity. The 3D QSAR, molecular fields (CoMFA, Rα2 = 0.999, Qα2 = 0.679, Rα-pred2 = 0.678 and Rβ2 = 0.999, Qβ2 = 0.611, Rβ-pred2 = 0.691) and similarity (CoMSIA, Rα2 = 0.999, Qα2 = 0.670, Rα-pred2 = 0.686 and Rβ2 = 0.999, Qβ2 = 0.671, Rβ-pred2 = 0.590) analyses show contour maps of steric, hydrophobic along with hydrogen bond (HB) donor and acceptor are important factors for binding affinity to both α- and β-subtypes. In addition, electronic contribution is crucial for α-subtype binding. Pharmacophore models derive the importance of HB acceptor and donor, aromatic ring, molecular steric, and hydrophobic interactions for selective binding to receptor subtypes. The derived models are correlated with structure-based molecular docking study, explaining the significant interactions between receptor and ligand for selective subtypes binding. Open image in new window Fig. 1 General structure of diarylpropionitrile scaffold. Common atoms are numbered through 1–14
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Molecular modeling studies on Structural Requirement of diarylpropionitrile for selectivity to estrogen receptor subtypes
Medicinal Chemistry Research, 2012Co-Authors: Md Ataul Islam, Ria Pal, Tabassum Hossain, Arup Mukherjee, Achintya SahaAbstract:Molecular modeling techniques are widely used to discover drug candidates for selective disease. In the present study, ligand-based drug design techniques have been explored to find the Structural Requirement of diarylpropionitrile derivatives, a group of non-steroidal estrogen receptor (ER) modulators for selective binding to receptor subtypes. 2D/3D quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies have been explored for this purpose. The classical QSAR models ( R _α ^2 = 0.870, Q _α ^2 = 0.813, R _α-pred ^2 = 0.636; R _β ^2 = 0.853, Q _β ^2 = 0.745, R _β-pred ^2 = 0.565) show the importance of molecular refractivity, electronic contribution of atoms C_3, C_7, C_13 and C_14, and R_2 and R_4 substituents (Fig. 1 ) for specificity. The 3D QSAR, molecular fields (CoMFA, R _α ^2 = 0.999, Q _α ^2 = 0.679, R _α-pred ^2 = 0.678 and R _β ^2 = 0.999, Q _β ^2 = 0.611, R _β-pred ^2 = 0.691) and similarity (CoMSIA, R _α ^2 = 0.999, Q _α ^2 = 0.670, R _α-pred ^2 = 0.686 and R _β ^2 = 0.999, Q _β ^2 = 0.671, R _β-pred ^2 = 0.590) analyses show contour maps of steric, hydrophobic along with hydrogen bond (HB) donor and acceptor are important factors for binding affinity to both α- and β-subtypes. In addition, electronic contribution is crucial for α-subtype binding. Pharmacophore models derive the importance of HB acceptor and donor, aromatic ring, molecular steric, and hydrophobic interactions for selective binding to receptor subtypes. The derived models are correlated with structure-based molecular docking study, explaining the significant interactions between receptor and ligand for selective subtypes binding. Fig. 1 General structure of diarylpropionitrile scaffold. Common atoms are numbered through 1–14
Kazuho Abe - One of the best experts on this subject based on the ideXlab platform.
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Structural Requirement for axonal regeneration promoting effect of polyamines in cultured rat hippocampal neurons
Brain Research, 1997Co-Authors: Kazuho Abe, Peng-jiang Chu, Akira Shirahata, Keijiro Samejima, Hiroshi SaitoAbstract:Abstract We have previously found that spermine, spermidine and putrescine promote axonal regeneration following axotomy in cultured rat hippocampal neurons. In the present study, we investigated which part of the polyamine molecule is responsible for the regeneration-promoting effect. Testing the effects of several synthetic analogues revealed that the butanediamine moiety is essential for the activity and the terminal primary amines are necessary for full agonist activity. The structure–activity relationship indicates that the regeneration-promoting effects of polyamines are not associated with NMDA receptors.
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Structural Requirement for neurotrophic activity of spermine in cultured rat hippocampal neurons
Japanese journal of pharmacology, 1995Co-Authors: Peng-jiang Chu, Akira Shirahata, Keijiro Samejima, Hiroshi Saito, Kazuho AbeAbstract:We investigated the structure-activity relationship for the neurotrophic activity of spermine by comparing the effects of several synthetic spermine analogues on the survival of cultured rat hippocampal neurons. N, N'' -bis(3-aminopropyl)-1, 6-hexanediamine and N, N'' -bis(3-aminopropyl)-1, 3-propanediamine did not promote the neuronal survival, suggesting that the central butanediamine structure is essential for the neurotrophic activity. Furthermore, N1, N12-bis(ethyl)spermine significantly promoted the neuron survival, but its maximum effect was smaller than that of spermine, indicating that two terminal primary amines are required for full agonist activity. The Structural Requirement for the neurotrophic activity of spermine was different from those for any other reported activities of polyamines.
