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 Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>