CoMFA and CoMSIA Studies on 5-hydroxyindole-3-carboxylate Derivatives as 5-lipoxygenase Inhibitors: Generation of Homology Model and Docking Studies

In this study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 2-substituted 5-hydroxyindole-3-carboxylate derivatives as potent 5-LOX inhibitorswith IC50 values ranging from 0.031 to 13.4 µM. Two datasets of same molecules were prepared with two different partial atomic charges; one with Gasteiger-Huckel and another with … Continued

Quantitative Structure-activity Relationship Studies of Threo-methylphenidate Analogs

Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to … Continued

3D-QSAR and Docking Studies on the Neuronal Choline Transporter

The high affinity neuronal choline transporter (CHT1) is responsible for the uptake of choline into the pre-synaptic terminal of cholinergic neurons. Considering our past experience with modeling the blood-brain barrier choline transporter (BBBCHT) as drug delivery vector to the CNS, we investigated the 3-D-quantitative structure-activity relationship of the neuronal choline transporter.  

Novel Analogs of Istaroxime, a Potent Inhibitor of Na(+),K(+)-ATPase: Synthesis, Structure-activity Relationship, and 3D-quantitative Structure-activity Relationship of Derivatives at Position 6 on the Androstane Scaffold

We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na(+),K(+)-ATPase. We explored the chemical space around the position 6 of the steroidalscaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3.

3D-QSAR and Docking Studies on Transforming Growth Factor (TGF)-β Receptor 1 Antagonists

The transforming growth factor-β (TGF-β) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-β, especially the subtype 1 receptor (TGBR1) kinase, no 3D-quantitiative structure-activity relationship study … Continued

CoMFA Analysis of tgDHFR and rlDHFR Based on Antifolates with 6-5 Fused Ring System Using the All-orientation Search (AOS) Routine and a Modified Cross-validated r2-guided Region Selection (q2)-GRS) Routine and Its Initial Application

We report the development of CoMFA analysis models that correlate the 3D chemical structures of 80 compounds with 6-5 fused ring system synthesized in our laboratory and their inhibitory potencies against tgDHFR and rlDHFR. In addition to conventional CoMFA analysis, we used two routines available in the literature aimed at the optimization of CoMFA: all-orientation … Continued

Predictive Screening Model for Potential Vector-mediated Transport of Cationic Substrates at the Blood-brain Barrier Choline Transporter

A set of semi-rigid cyclic and acyclic bis-quaternary ammonium analogs, which were part of a drug discovery program aimed at identifying antagonists at neuronal nicotinic acetylcholine receptors, were investigated to determine structural requirements for affinity at the blood-brain barrier choline transporter (BBB CHT). This transporter may have utility as a drug delivery vector for cationic … Continued

Comparative Molecular Field Analysis of Fenoterol Derivatives: A Platform Towards Highly Selective and Effective β(2)-adrenergic Receptor Agonists

The purpose of this study was to use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the β(2)-adrenergic receptor. Out of 21 computationally designed structures, 6 compounds were synthesized and characterized for β(2)-AR binding affinities, subtype selectivities and functional activities.  

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