In recent years an effort has been made to supplement traditional methods for drug discovery by computer-assisted “structure-based design.” The structure-based approach involves (among other issues) reasoning about the geometry of drug molecules (or ligands) and about the different spatial conformations that these molecules can attain. This is a preliminary report on a set of tools that we are ...

histone deacetylase inhibitors have gained a great deal of attention recently for the treatment of cancers and inflammatory diseases. so design of new inhibitors is of great importance in pharmaceutical industries and labs. creating pharmacophor models in order to design new molecules or search a library for finding lead compounds is of great interest. this approach reduces the overall cost ass...

The ginkgolides represent a challenge for the organic chemist owing to their unique cage structure and their high potential biological activity. They were found to be potential PAF antagonists. The results of studies carried out in our laboratory are discussed, leading to conclusions on ginkgolides quantitative structure±activity relationship by using CoMFA and the probable pharmacophore and th...

N a g a k u m a r B h a r a t h a m e t a l. N a g a k u m a r B h a r a t h a m , K a v i t h a B h a r a t h a m ,

Protein kinase is a novel therapeutic target for human diseases. The off-target and side effects of ATP-competitive inhibitors preclude them from the clinically relevant drugs. The compounds targeting the druggable allosteric sites outside the highly conversed ATP binding pocket have been identified as promising alternatives to overcome current barriers of ATP-competitive inhibitors. By simulta...

• Modified peptides: these molecules contain relatively small modifications that do not modify the peptide bond, and thus they still possess a chemical structure of peptide nature. • Pseudopeptides: in these compounds partial modifications of either peptide bonds or side-chains are introduced, contributing to the generation of molecules possessing a chemical structure of only partial peptide na...

The formylpeptide receptor (FPR) family of G-protein-coupled receptors contributes to the localization and activation of tissue-damaging leukocytes at sites of chronic inflammation. We developed a FPR homology model and pharmacophore (based on the bovine rhodopsin crystal structure and known FPR ligands, respectively) for in silico screening of approximately 480,000 drug-like small molecules. A...

Plasmodium falciparum subtilisin-like protease 1 (SUB1) is a novel target for the development of innovative antimalarials. We recently described the first potent difluorostatone-based inhibitors of the enzyme ((4S)-(N-((N-acetyl-l-lysyl)-l-isoleucyl-l-threonyl-l-alanyl)-2,2-difluoro-3-oxo-4-aminopentanoyl)glycine (1) and (4S)-(N-((N-acetyl-l-isoleucyl)-l-threonyl-l-alanylamino)-2,2-difluoro-3-o...