Jean-Charles Quirion

Indole monoterpene alkaloids from leaves of Psychotria suterella Müll. Arg. (Rubiaceae)

1. Subject and sourcePsychotriasuterellaMuull. Arg. (Rubiaceae) is a shrub or small tree ofup to 2m in.height, that is found in coastal tropical forests of Southern Brazil, ranging from RiodeJaneirotoRioGrandedoSul(DillemburgandPorto,1985).PlantswerecollectedintheruralareaofthecityofTreesForquilhas,RS,Brazil,inthesummerof1999and#identified by botanist Marcos Sobral (Faculty ofPharmacy, Universidade Federaldo Rio Grande do Sul-UFRGS). A voucher specimen (ICN 98870) has beendeposited in the UFRGS herbarium.2. Previous workPsychotria (Rubiaceae) is a complex genus, with estimates of1000–1650 species(Nepokroeff et al., 1999). Segregation ofspecies into new genera has been proposedbased on molecular and morphological analyses (Nepokroeff et al., 1999; Taylor,

Straightforward Preparation of Functionalized α‐CF2‐Galactosides through an Oxygen to Carbon Acyl Migration

A high number of O-glycoconjugates of therapeutic interest feature an a-galactose or 2-deoxy-2-acetamido-a-galactose unit in their structure, often serving as the link between the aglycon and the glycosidic parts. For example, this motif is found in tumor-associated antigens, antifreeze glycoproteins (AFGP) or in immunoregulative a-galactosylceramides. This last family of glycosphingolipids (agelasphins) exhibit strong in vivo activities against infectious diseases and tumor metastases, which were found to be related to their immunoregulative properties.

Synthesis of fluorinated C-mannopeptides as sialyl Lewisx mimics for E- and P-selectin inhibition

The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH(2)-glycopeptides already reported to act as sLe(x) mimics. The alpha and beta anomers of these CF(2)-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of alpha- and beta-pyranose and alpha- and beta-furanose forms. These molecules showed inhibitory activities comparable to their CH(2) counterparts with a moderate influence of the pseudo-anomeric center configuration.

Peptídeos de conformação restrita induzida pela incorporação de unidades (aza)lactâmicas

Conformational constraint is an approach which can be used to restrict the flexibility of peptide molecules and to provide information on the topographical requirements of receptors. The incorporation of conformationally constrained units in a peptide can lead to peptide analogues that present numerous advantages such as the potentialization of the pharmacological activity and the decrease of enzymatic degradation. This review discusses the peptide analogues containing a lactam or azalactam unit in their sequences. Of particular interest has been the replacement of a dipeptide motif in a peptide that simulates a b-turn.

Abstract LB-201: New derivatives of etoposide show promise as more potent inhibitors of cancer cell growth

The DNA repair enzyme Topoisomerase II (TopoII) has been recognized in the oncology field as a clinically important therapeutic target for a variety of cancers. The class of agents known as etoposides were specifically designed with this target in mind. Etoposides lacked the major problem of cardiac toxicity associated with the anthracyclines class of drugs (e.g. doxorubicin). Sunshine Biopharma has recognized that the reduced efficacy and high toxicity of etoposide are due to instability of the molecule leading to a conversion of the drug which then functions as a tubulin inhibitor rather than a TopoII inhibitor (unpublished observations). Accordingly, the company set out to develop a true TopoII inhibitor and these efforts have yielded two compounds called Adva-27a and Adva-32a. These drugs and their derivatives have been described in US Patent Application Number: 20090318675. Using cell lines derived from a variety of human cancers, Adva-27a is almost always a more potent inhibitor of cell growth compared to etoposide, and cells expressing the MDR-drug resistance protein are very sensitive to this drug. Furthermore, consistent with the literature, amplification of the TOP2α gene is associated with increased sensitivity to growth inhibition. The preliminary data show that in all but the brain tumor cell line, increased TOP2α copy number is associated with even greater percent inhibition by Adva-27a versus etoposide regardless of the tissue of origin of the tumor cell lines. This data and plans for further analysis of these drugs will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-201. doi:10.1158/1538-7445.AM2011-LB-201

Attempts at asymmetric electrosynthesis of α-fluorinated cyclopropylphosphonamides

Variously N,N-disubstituted chiral dibromofluoromethylphosphonamides 3 were easily prepared and used for the asymmetric electrosynthesis, in the presence of tert-butyl acrylate, of α-fluorinated cyclopropylphosphonamides 7. The diastereoisomeric excesses are moderate (up to 40%). Moreover, the identification of the trans and cis stereoisomers has been deduced from analysis of 2D 1H–19F HOESY spectra.