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University Of Agricultural Science And Veterinary Medicine Cluj Napoca
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Papers by kirti sarbhai
SAR and QSAR in Environmental Research, 2011
Selective human serotonin reuptake transporter (hSERT) inhibition is the first line of treatment ... more Selective human serotonin reuptake transporter (hSERT) inhibition is the first line of treatment to deal with the depression. In clinical practice for managing depression, the stimulants are co-prescribed to overcome cognitive impairment and fatigue. Recently, histamine H(3) antagonists with serotonin reuptake inhibition activity have been proposed as alternative approach for the treatment of depression. In this context, a QSAR study of hSERT inhibitory and H(3) antagonistic activity of piperazine and diazepane amide derivatives has been carried out using the combinatorial protocol in multiple linear regression (CP-MLR) with 0D- to 2D-Dragon descriptors. The derived QSAR models have provided a rational approach for the development of new piperazine and diazepane amide derivatives as hSERT inhibitors and H(3) antagonists. In a concomitant partial least-squares (PLS) analysis of the hSERT and histamine H(3) activities, the fraction contributions of identified descriptors revealed their importance in modulating these activities. The PLS analysis of other biological endpoints, namely hNET, hDAT, and histamine H(3) activity in functional assay (H(3)pA(2)) of these analogues with the identified descriptors has further highlighted their scope in modulating these activities.
The 5-HT7 receptor binding affinity of (phenylpiperazinyl-alkyl)oxindole derivatives are quantita... more The 5-HT7 receptor binding affinity of (phenylpiperazinyl-alkyl)oxindole derivatives are quantitatively studied using Fujita-Ban and Hansch type analyses. The Fujita-Ban study resulted in the contributions of different substituents and the parent moiety for the binding affinity. The substituents that have a higher positive contribution to the given activity, relative to substituents of the parent moiety at different positions were then used to obtain a trend for the active analogues. None of the R1 substituents present at 5-, 6- and 7- positions appears to be advantageous over the substituents of the parent moiety for 5-HT7 binding affinity. Similarly, the 3'-substituents of R2 and spacer (n = 5) do not contribute positively to the activity. However, the Y-substitution and 4'-R2 substituents contribute positively to the activity and certainly improve inhibitory actions of the compounds. The appropriate substituents for varying positions, which have highest positive contribut...
Journal of Enzyme Inhibition and Medicinal Chemistry, 2008
![Research paper thumbnail of A Rationale for the Activity Profile of Arylpiperazinylthioalkyls As 5-HT1A-Serotonin and [Alpha] 1-Adrenergic Receptor Ligands](https://attachments.academia-assets.com/72695017/thumbnails/1.jpg)
](European journal of medicinal chemistry, 2010
The 5-HT 1A and a 1-receptor binding affinities of the arylpiperazinylthioalkyl derivatives have ... more The 5-HT 1A and a 1-receptor binding affinities of the arylpiperazinylthioalkyl derivatives have been quantitatively expressed in terms of topological and molecular features. The analysis revealed that a lower value of atomic composition based index (AAC), higher values of structural information content (SIC3) and topological charge index (GGI9) would be beneficial to the 5-HT 1A receptor binding. For the a 1-receptor binding affinity the higher values of topological charge index (GGI9) and atomic Sanderson electronegativities weighted descriptor (GATS3e) and more number of hydrogen atoms attached to sp or sp 3 hybridized carbon atoms in a molecular structure (H-047) would be favorable. The derived significant models may further be used to synthesize new potential and selective compounds.
Molecular Diversity, 2011
The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine d... more The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine derivatives have been analyzed based on topological and molecular features. Analysis of the structural features in conjunction with the biological endpoints in Combinatorial Protocol in Multiple Linear Regression (CP-MLR) led to the identification of 21 descriptors for modeling the activity. The study clearly suggested that the role of Randic
Molecular Diversity, 2010
The carbonic anhydrase inhibition activities of sulfonamide and sulfamate derivatives have been q... more The carbonic anhydrase inhibition activities of sulfonamide and sulfamate derivatives have been quantitatively expressed in terms of MOE descriptors representing the 2D-features of compounds following combinatorial protocol in multiple linear regression (CP-MLR). The derived QSAR models have shown that partially charged and polarized surface areas in particular ranges, hydrophobicity, connectivity, information content, van der Waals surface area of the pharmacophore,
SAR and QSAR in Environmental Research, 2011
Selective human serotonin reuptake transporter (hSERT) inhibition is the first line of treatment ... more Selective human serotonin reuptake transporter (hSERT) inhibition is the first line of treatment to deal with the depression. In clinical practice for managing depression, the stimulants are co-prescribed to overcome cognitive impairment and fatigue. Recently, histamine H(3) antagonists with serotonin reuptake inhibition activity have been proposed as alternative approach for the treatment of depression. In this context, a QSAR study of hSERT inhibitory and H(3) antagonistic activity of piperazine and diazepane amide derivatives has been carried out using the combinatorial protocol in multiple linear regression (CP-MLR) with 0D- to 2D-Dragon descriptors. The derived QSAR models have provided a rational approach for the development of new piperazine and diazepane amide derivatives as hSERT inhibitors and H(3) antagonists. In a concomitant partial least-squares (PLS) analysis of the hSERT and histamine H(3) activities, the fraction contributions of identified descriptors revealed their importance in modulating these activities. The PLS analysis of other biological endpoints, namely hNET, hDAT, and histamine H(3) activity in functional assay (H(3)pA(2)) of these analogues with the identified descriptors has further highlighted their scope in modulating these activities.
The 5-HT7 receptor binding affinity of (phenylpiperazinyl-alkyl)oxindole derivatives are quantita... more The 5-HT7 receptor binding affinity of (phenylpiperazinyl-alkyl)oxindole derivatives are quantitatively studied using Fujita-Ban and Hansch type analyses. The Fujita-Ban study resulted in the contributions of different substituents and the parent moiety for the binding affinity. The substituents that have a higher positive contribution to the given activity, relative to substituents of the parent moiety at different positions were then used to obtain a trend for the active analogues. None of the R1 substituents present at 5-, 6- and 7- positions appears to be advantageous over the substituents of the parent moiety for 5-HT7 binding affinity. Similarly, the 3'-substituents of R2 and spacer (n = 5) do not contribute positively to the activity. However, the Y-substitution and 4'-R2 substituents contribute positively to the activity and certainly improve inhibitory actions of the compounds. The appropriate substituents for varying positions, which have highest positive contribut...
Journal of Enzyme Inhibition and Medicinal Chemistry, 2008
European journal of medicinal chemistry, 2010
The 5-HT 1A and a 1-receptor binding affinities of the arylpiperazinylthioalkyl derivatives have ... more The 5-HT 1A and a 1-receptor binding affinities of the arylpiperazinylthioalkyl derivatives have been quantitatively expressed in terms of topological and molecular features. The analysis revealed that a lower value of atomic composition based index (AAC), higher values of structural information content (SIC3) and topological charge index (GGI9) would be beneficial to the 5-HT 1A receptor binding. For the a 1-receptor binding affinity the higher values of topological charge index (GGI9) and atomic Sanderson electronegativities weighted descriptor (GATS3e) and more number of hydrogen atoms attached to sp or sp 3 hybridized carbon atoms in a molecular structure (H-047) would be favorable. The derived significant models may further be used to synthesize new potential and selective compounds.
Molecular Diversity, 2011
The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine d... more The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine derivatives have been analyzed based on topological and molecular features. Analysis of the structural features in conjunction with the biological endpoints in Combinatorial Protocol in Multiple Linear Regression (CP-MLR) led to the identification of 21 descriptors for modeling the activity. The study clearly suggested that the role of Randic
Molecular Diversity, 2010
The carbonic anhydrase inhibition activities of sulfonamide and sulfamate derivatives have been q... more The carbonic anhydrase inhibition activities of sulfonamide and sulfamate derivatives have been quantitatively expressed in terms of MOE descriptors representing the 2D-features of compounds following combinatorial protocol in multiple linear regression (CP-MLR). The derived QSAR models have shown that partially charged and polarized surface areas in particular ranges, hydrophobicity, connectivity, information content, van der Waals surface area of the pharmacophore,