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
Publication: Bioorganic & Medicinal Chemistry Letters
3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. The CoMFA and CoMSIA models using 54 molecules in the training set, gave rcv2 values of 0.644 and 0.507, r2 values of 0.959 and 0.951, respectively.
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
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.
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.
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
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
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
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.
Vitamin E (VE) is a generic term that represents a family of compounds composed of various tocopherol and tocotrienolisoforms. Tocotrienols display potent anti-angiogenic and antiproliferative activities.