In this study an attempt was made to understand the structural requirements for Topoisomerase I (Topo I) inhibition using a novel Group based QSAR (GQSAR) or fragment based QSAR technique. Here we combined the GQSAR technology with conventional 2D and 3D QSAR to derive GQSAR models for various reported naphthoquinone derivatives. Various regression models such as Multiple Regression (MRA), Part...

Several small-molecule CDK inhibitors have been identified, but none have been approved for clinical use in the past few years. A new series of 4-[(3-hydroxybenzylamino)-methylene]-4H-isoquinoline-1,3-diones were reported as highly potent and selective CDK4 inhibitors. In order to find more potent CDK4 inhibitors, the interactions between these novel isoquinoline-1,3-diones and cyclin-dependent...

UNLABELLED BACKGROUND Coronary heart disease continues to be the leading cause of mortality and a significant cause of morbidity and account for nearly 30% of all deaths each year worldwide. High levels of cholesterol are an important risk factor for coronary heart disease. The blockage of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity by small molecule inhibitors has bee...

The present study describes the implementation of a new three-dimensional quantitative structure-activity relationship (3D-QSAR) technique: comparative molecular similarity indices analysis (CoMSIA) to a set of novel herbicidal sulfonylureas targeted acetolactate synthase. Field expressions in terms of similarity indices in CoMSIA were applied instead of the usually used Lennard-Jones and Coulo...

During the last year we have developed Open3DQSAR, an open-source tool aimed at high-throughput 3DQSAR model building and evaluation [1]. During development, high performance and ease of automation were defined as primary goals; the first was achieved by implementation of parallelized algorithms and the second by adopting a scriptable interface. Molecular interaction fields of different kinds (...

A series of 42 Pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors regarded as promising antitumor agents to complement the existing therapies, was subjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSAR methods, comparative molecular field analysis (CoMFA), CoMFA region focusing, and comparative molecular similarity indice...

CDK2 is a promising target for the development of anti-cancer agents. It is not an easy task to design CDK2-selective inhibitors which do not exhibit activity for other CDK family members, particularly CDK4, due to a high degree of structural homology among CDK family members. In this study, 4-substituted N-phenylpyrimidin-2-amine derivatives as CDK2 inhibitors were examined to understand the s...

Research and development of multi-target inhibitors has attracted increasing attention as anticancer therapeutics. B-RafV600E synergistically works with vascular endothelial growth factor receptor 2 (KDR) to promote the occurrence and progression of cancers, and the development of dual-target drugs simultaneously against these two kinds of kinase may offer a better treatment advantage. In this ...

Combretastatin A-4 (CA-4) is one of the most potent tubulin polymerization inhibitors. In this paper, the identification of some new CA-4 analogues as potential tubulin polymerization inhibitors is performed by combination of molecular modeling techniques including 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. The built 3D-QSAR models show significant statistical quality an...

The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. A combined study of 3D-QSAR and molecular docking has been undertaken to explore the structural insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved comparative molecular field analysis (CoMFA) and comparative molecular similarity ...