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 Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>