Synthesis, characterization and potential application of monoacyl-cyclodextrins.

Although the preparation of cyclodextrin (CD) monoesters with a variety of carboxylic acids has been already described in the literature, the direct regioselective CD acylation has proved to be critical, often requiring to be replaced with a more elaborate synthetic process. In this paper we describe the one-step preparation of several monoacylated CDs from acyclic or aromatic carboxylic acid derivatives. The ability of beta-CD to enclose cupric ions in a sandwich-type manner was exploited to lead to high regioselectivity in the acylation of beta-CD with benzoyl chloride, cinnamoyl chloride and phenyl acetyl chloride in water.

Inhibition of farnesyltransferase: a rational approach to treat cancer?

This article presents in brief the development of farnesyltransferase inhibitors (FTIs) and their preclinical and clinical status. In this review the mechanism of action of FTIs is discussed and their selectivity issue towards tumor cells is also addressed. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in Clinical Phase II-III studies.

Insights into the structural requirements of farnesyltransferase inhibitors as potential anti-tumor agents based on 3D-QSAR CoMFA and CoMSIA models.

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on three different chemical series reported as selective farnesyltransferase (FTase) inhibitors employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) techniques to investigate the structural requirements for substrates and derive a predictive model that may be used for the design of novel FTase inhibitors. Removal of outliers improved the predictive power of models developed for all three structurally diverse classes of compounds. 3D-QSAR models were derived for 3-aminopyrrolidinone derivatives (training set N=38, test set N=7), 2-amino-nicotinonitriles (training set N=46, test set N=13) and 1-aryl-1'-imidazolyl methyl ethers (training set N=35, test set N=5).

Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: search for better COX-2 inhibitors.

A series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazole N-oxides were prepared and evaluated for COX-2 and COX-1 binding affinity in vitro and for antiinflammatory activity by the rat paw edema method. p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazole N-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 micromol L(-1) and COX-1 enzyme inhibition of 44% at 88 micromol L(-1) concentrations, but showed very low in vivo anti-inflammatory activity.

3D-QSAR CoMFA/CoMSIA studies on 5-aryl-2,2-dialkyl-4-phenyl-3(2H)-furanone derivatives, as selective COX-2 inhibitors.

Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on a series of 5-aryl-2,2-dialkyl-4-phenyl-3(2H)-furanone derivatives, as selective cyclooxygenase-2 (COX-2) inhibitors. Ligand molecular superimposition on the template structure was performed by the atom/shape based root mean square fit and database alignment methods. Removal of three outliers from the initial training set of 49 molecules improved the predictivity of the model.