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 New Computer Model Could Explain how Simple Molecules Took First Step Toward Life
29.07.2015 | Brookhaven National Laboratory

nachricht Switch for building barrier in roots
29.07.2015 | The University of Tokyo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

Im Focus: Smarter window materials can control light and energy

Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.

By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...

Im Focus: Simulations lead to design of near-frictionless material

Argonne scientists used Mira to identify and improve a new mechanism for eliminating friction, which fed into the development of a hybrid material that exhibited superlubricity at the macroscale for the first time. Argonne Leadership Computing Facility (ALCF) researchers helped enable the groundbreaking simulations by overcoming a performance bottleneck that doubled the speed of the team's code.

While reviewing the simulation results of a promising new lubricant material, Argonne researcher Sanket Deshmukh stumbled upon a phenomenon that had never been...

Im Focus: NASA satellite camera provides 'EPIC' view of Earth

A NASA camera on the Deep Space Climate Observatory (DSCOVR) satellite has returned its first view of the entire sunlit side of Earth from one million miles away.

The color images of Earth from NASA's Earth Polychromatic Imaging Camera (EPIC) are generated by combining three separate images to create a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

A New Litmus Test for Chaos?

29.07.2015 | Physics and Astronomy

New Computer Model Could Explain how Simple Molecules Took First Step Toward Life

29.07.2015 | Life Sciences

New ERC calls published under Horizon 2020

29.07.2015 | Awards Funding

VideoLinks
B2B-VideoLinks
More VideoLinks >>>