RSC Medicinal Chemistry Blog

In this Hot article, scientists from France present a self-immolative dendritic glucuronide prodrug designed for the release of two doxorubicin molecules after a single triggering event.

‘While numerous glucuronide prodrugs have been studied so far, the efficiency of this targeting strategy is limited by the poor turnover of beta-glucuronidase in malignant tissues. Our novel dendritic prodrug which is programmed to release two molecules of doxorubicin after a single enzymatic activation step may permit to overcome this drawback’, the authors explain.

The biological experiments conducted have shown that this novel enzyme-responsive dendritic prodrug is twice more toxic than its monomeric counterpart against H661 lung cancer cells. It is hoped that this novel approach may open new avenues in selective cancer chemotherapy.

Selected as HOT, read this article for free now.

A self-immolative dendritic glucuronide prodrug of doxorubicin
Marion Grinda, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy-Opalinski and Sébastien Papot
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00193K, Concise Article

Work from this international collaboration spanning Denmark, Italy, Sweden and the USA brings insights into the synthesis and characterization of a selective agonist for the metabotropic glutamate receptor mGluR2, a potential therapeutic target for neurologic and psychiatric diseases.

The team’s approach to the agonist design was to induce selectivity for mGluR2 over other family members via imposing conformational rigidity into the carbon skeleton of the Glu analogues. This resulted in an increase of selectivity of at least two orders of magnitude compared to homologous mGluR3 as well as mGluR1, 4, 5, 7.

A highly selective agonist for the metabotropic glutamate receptor mGluR2
Simon D. Nielsen, Marica Fulco, Michaela Serpi, Birgitte Nielsen, Maria B. Hansen, Kasper L. Hansen, Christian Thomsen, Robb Brodbeck, Hans Bräuner-Osborne, Roberto Pellicciari, Per-Ola Norrby, Jeremy R. Greenwood and Rasmus P. Clausen

Interested? Why not read this MedChemComm article now! All our content is currently FREE to access .

Coronary heart disease has been shown to be related to low levels of high-density lipoprotein cholesterol (HDL-C) in blood plasma, and consequently methods of controlling HDL-C levels are sought to reduce the risk of heart disease.  Inhibition of the cholesteryl ester transfer protein (CETP) – the protein that transports cholesteryl esters from high-density lipoprotein (HDL) to low- and very low-density lipoproteins (LDLs and VLDLs) – has shown potential as a therapy.

Tarun Jha and a team from Jadavpur University have performed studies on a series of 2-arylbenzoxazoles to define the structural requirements of a good CETP inhibitor.  The 2D QSAR study using using PCR, PLS and MLR techniques and kNN-MFA 3D QSAR results have generated a pharmacophore that they hope will provide a good scaffold for the design of future potent CETP inhibitors.

Download the paper today to read the details of their findings – it’s free to access until the end of 2011:

Chemometric modeling and pharmacophore mapping in coronary heart disease: 2-arylbenzoxazoles as cholesteryl ester transfer protein inhibitors
Dhritiman Jana, Amit Kumar Halder, Nilanjan Adhikari, Milan Kumar Maiti, Chanchal Mondal and Tarun Jha
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00135C