Dear Marcus,

I have read a very interesting paper on Filtering promiscuous compounds in early drug discovery: is it a good idea? Posted on March 14, 2016 by SDDC which sheds light on the topic of concern.Herein some importantparagraphs from the article regarding quinones:

This is the question posed by the authors of a recent Drug Discovery Today article (Senger et al, Drug Discovery Today, article in press ). On first reading the question the instant answer from most practising medicinal chemists is surely yes, however the authors make some very good points that eliminating certain groups such as indoles from screening collection is somewhat short sighted or just simply wrong. On the other hand the authors do make some rather surprising and possibly naïve statement such as the recommendation to include quinone structures in phenotypic screening collections, an experienced medicinal chemist would argue there is simply no point testing them as they will be active anyway!

The article highlights the difference between classical biochemical screening with the objective of identifying hits which are active against a single target and phenotypic screening where the objective is to identify functionally active compounds irrespective of their mechanism of action. The authors propose that the now popular PAINS filters (Nature 2014, 513, 481-483) are appropriate for biochemical screening but should not be applied to compound collections used for phenotypic screening. They highlight a number of examples of structural types which are present in known drugs but would be removed by applying PAINS filters for example quinones (table 1). It is true that there are many quinone containing drugs on the market, but it is difficult to agree with the recommendation that even in phenotypic screens such compounds should be included. The compounds simply work by scavenging electrons and given the number of marketed drugs that contain quinones there is little need for more. Perhaps the only justification is to include marketed drugs in phenotypic screening collections with a view to future repositioning.

For more details and to view table 1, please use the following link:

https://sussexdrugdiscovery.wordpress.com/

Hoping this will be helpful,

Rafik

Thanks for your anwser Rafik. I've read that paper and in fact I know some of the authors. Reading more about it I agree that simply discarding some compounds is short sighted but for quinones... no, I really don't like them. I had my first contact with molecules like this last year as anticancer, now as antibacterial etc. I can see quinones everywhere but the literature supporting promiscuity and toxicity is so strong I think it is best not to screen such compounds for everything (as this is common place in my country).

Interesting discussion on the subject:

http://blogs.sciencemag.org/pipeline/archives/2016/02/23/bright-chemical-matter

Our company is focusing on redox active molecules as an drug. Currently, we have two drugs in Phase 2/2b. Check it out our company website.

http://www.bioelectron.com/

Article Vitamin E hydroquinone is an endogenous regulator of ferropt...