Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Making the Good Much Better Against Cancer

10.03.2014

Synthesis, Anti-tubulin and Antiproliferative Structure–Activity Relationship of Steroidomimetic Dihydroisoquinolinones

Tubulin, the building-block protein of cellular microtubules, is a well-validated cancer drug target: Disrupting tubulin polymerization affects cytoskeletal function and thus cell division. The vinca alkaloids, taxanes, and other taxane site binders have found wide therapeutic application and constitute one of the most successful classes of anticancer agent.


Nevertheless, current drugs that target tubulin still suffer from limited therapeutic window, acquired resistance, lack of oral bioavailability, and problematic formulation.

As reported in ChemMedChem, Barry Potter’s research group at the University of Bath (UK), along with colleagues at the NCI (USA), Ipsen (France), and Imperial College London, focused on a natural steroidal lead for introducing a new set of modifications that confer good oral activity and delivery and that impart resistance to metabolism.

"Two compounds showed in vitro anti-angiogenic activity, and X-ray analysis of one reveals that electrostatic repulsion between two adjacent carbonyl groups [...] dictates adoption of a 'steroid-like' conformation that might partially explain the excellent in vitro activities," says Potter. Indeed, the most active compounds are nearly equivalent to another compound currently in clinical trials as inhibitors of tubulin assembly, and some were shown to be anti-angiogenic. Moreover, the compounds are easily synthesized and amenable to aqueous formulation.

About the Author

Professor Barry Potter holds the established chair of Medicinal Chemistry at the University of Bath and is also Visiting Professor of Medicinal Chemistry at Oxford University. His research interests are in mechanistic enzymology, the chemistry of signal transduction, and anticancer drug design and discovery, and he has brought academically discovered drugs to multiple clinical trials. He is a Fellow of the Royal Society of Chemistry (RSC) and the Society of Biology, was elected to the UK National Academy of Medical Sciences, has won four interdisciplinary RSC medals, the GlaxoSmithKline International Achievement Award, and was named Investigator of the Year at the 2012 European Life Science Awards.

Author: Barry V. L. Potter, University of Bath (UK), http://www.bath.ac.uk/pharmacy/contacts/academics/barry_potter/

Title: Synthesis, Anti-tubulin and Antiproliferative SAR of Steroidomimetic Dihydroisoquinolinones

ChemMedChem, Permalink to the article: http://dx.doi.org/10.1002/cmdc.201400017

Barry V. L. Potter | Wiley VCH

Further reports about: Cancer RSC activity anti-angiogenic anticancer compounds drugs resistance therapeutic

More articles from Life Sciences:

nachricht Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Perfect imperfection
03.05.2016 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Quantum Logical Operations Realized with Single Photons

03.05.2016 | Physics and Astronomy

Discovery of a fundamental limit to the evolution of the genetic code

03.05.2016 | Life Sciences

Cavitation aggressive intensity greatly enhanced using pressure at bubble collapse region

03.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>