About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
Not Voodoo

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
Realizations in Biostatistics
ChemSpider Blog
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Eye on FDA
Chemical Forums
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa

Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
Gene Expression (I)
Gene Expression (II)
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net

Medical Blogs
DB's Medical Rants
Science-Based Medicine
Respectful Insolence
Diabetes Mine

Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem

Politics / Current Events
Virginia Postrel
Belmont Club
Mickey Kaus

Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Benlysta's Adventures In the Real World | Main | The CETP Saga Continues (And It's Not Getting More Entertaining) »

May 4, 2012

Cytotoxic? You Bet!

Email This Entry

Posted by Derek

Now these are the funkiest structures I've seen in quite a while. I won't spoil the surprise; if you're an organic chemist, go ahead and click on the link. This is one of those "No one's made compounds like this, so let's see if they do anything" papers, and I'd say that if you're going to do that sort of thing, you should go pretty far off the beaten path. That they have.

These compounds are - not surprisingly - said to be cytotoxic, with activity against a range of cancer cell lines. A couple of passes through the paper, and I haven't found any normal cells used as controls for all that cytotoxicity. Sad to say, the betting would be that there's no window at all. But at least I've seen a class of compounds that I'll bet has never made it into J. Med. Chem. before.

Comments (28) + TrackBacks (0) | Category: Cancer | Chemical News


1. Curryworks on May 4, 2012 11:01 AM writes...

Bleach is the best anti-cancer agent known to man.

Permalink to Comment

2. Sherman on May 4, 2012 11:01 AM writes...

A question related to this... if you are doing only in vitro (cell line studies), what is considered the "best" model for normal cell toxicity?

I've seen 3T3s used a lot in academia, however, I also have heard plenty of people say that fibroblasts are a terrible model for normal cell toxicity.

What is preferred?

Permalink to Comment

3. Canageek on May 4, 2012 11:01 AM writes...

Bonus points for testing organometallic compounds.

Permalink to Comment

4. processchemist on May 4, 2012 11:05 AM writes...

@ 2

My friends in academia use HFF, and I heard that this cell line is still a standard in industry.

Permalink to Comment

5. Rogi on May 4, 2012 11:10 AM writes...

I would at least like to see them tested in a HTA to see if they would work as Fischer Tropsch catalysts or as Haber Bosch catalysts

Permalink to Comment

6. opsomath on May 4, 2012 11:15 AM writes...

Didn't they make ferrocenyl-for-phenyl switches in a lot of drugs not too long ago and find that they generally had the original activity, but were really toxic as a bonus? I seem to recall some kind of aspirin analogue causing cancer.

Permalink to Comment

7. gippgig on May 4, 2012 12:35 PM writes...

Note that the chemical formulas in the abstract are screwed up.
Try making the symmetrical compounds with a selenoamide on both ferrocene rings.
Some of these compounds might make interesting ligands (think dppf).

Permalink to Comment

8. Josh on May 4, 2012 12:53 PM writes...

Good lord. Organic compounds from Mars.

Permalink to Comment

9. Jon on May 4, 2012 1:01 PM writes...

I just wonder how bad a selenyl ketone smells.

For that matter, I wonder what kind of precautions they had to take to work with this stuff. I'd probably want a lab built for highly-potent compounds, perferably combined with a glovebox.

Permalink to Comment

10. Bruce Hamilton on May 4, 2012 1:03 PM writes...

They might be good octane enhancers for some gasolines, as Midgley found selenium compounds were similar to alkyl leads and ferrocene has been used as a octane enhancer. I think selenium was rejected for smell and toxicity reasons.

Fortunately the organometallic octane enhancers have been consigned to history in most countries.

Permalink to Comment

11. Dystopedon on May 4, 2012 1:22 PM writes...

Check out the names on that article. Mexicans are now making the chemicals Americans just won't make(with damn good reason, it looks like.)

Permalink to Comment

12. partial agonist on May 4, 2012 1:43 PM writes...

Sorry, but I have to say that this should not be in J Med Chem.

It may be decent chemistry (I did not take the time to look), but there is no medicinal chemistry there, if the endpoint is cytotoxicity and the authors did not even make the effort to try to determine if the cytotoxicity is seen in normal cells. The biological testing is thus an experiment with no appropriate control, which is thus for all practical purposes a non-experiment, because no usefulness is established whatsoever.

Permalink to Comment

13. Quintus on May 4, 2012 2:02 PM writes...

Did the Dinos make these?

Permalink to Comment

14. nitrosonium on May 4, 2012 2:14 PM writes...

@#2 and #4: yes. we use HFF cells as "normal" control cell in cell proliferation assays (WST-1)

Permalink to Comment

15. RD on May 4, 2012 2:31 PM writes...

Yeah, that wouldn't have made my HTS cut.

Permalink to Comment

16. Curious Wavefunction on May 4, 2012 2:37 PM writes...

@1: I would recommend ingesting a few milligrams of these, then drinking a solution of bleach to destroy the excess. After all you wouldn't want any side effects.

Permalink to Comment

17. Hap on May 4, 2012 3:11 PM writes...

I thought cytotoxins were a dime a dozen - it's compounds that don't actually kill the cells you want (but kill cancer cells) that aren't. So why wasn't the absence of cytotoxicity data in noncancerous cells in this paper (or even a statement that such was obtained) a problem? Or did I miss such a statement/data?

Permalink to Comment

18. Bitter reject on May 4, 2012 3:45 PM writes...

As has been discussed here recently further evidence of madness of j med chem referees and editors.

Permalink to Comment

19. Just1 on May 5, 2012 10:27 AM writes...

Another "high impact" paper from the "Instituto de QuĂ­mica"... Such a prank is however not very surprising for someone who knows how humble are the "Investigadores" working in that research center. The glorious Syntex times have gone, unfortunately.
@18: while referees are anonymous, no one can blame them. After all, maybe they didn't recommend releasing this piece.

Permalink to Comment

20. Iridium on May 5, 2012 11:25 AM writes...

Orally available?

I am sure the taste is great!!!!!!!!

Permalink to Comment

21. Nick K on May 5, 2012 11:28 AM writes...

This paper should NEVER have been published in J Med Chem - no controls whatever were used. As other posters have noted, cytotoxicity is completely worthless without selectivity for cancer cells. In any case, compared with "proper" antineoplastics, these compounds are only weak, micromolar agents. Did the authors try simple selenoamides in their assay to control for activity merely due to selenium toxicity?

Permalink to Comment

22. #7 on May 6, 2012 3:43 PM writes...

I agree this should be a flagship journal for our craft. Unfortunately the editors / associate editors really need to step up, as too much weak science is getting through.

Permalink to Comment

23. Hap on May 6, 2012 9:38 PM writes...

#21: I think they tried selenobenzamide as a control for selenium toxicity, but I have only looked at the paper yet.

Permalink to Comment

24. RB Woodweird on May 7, 2012 6:18 AM writes...

1. This probably smells like dog turds left to ferment in a vat of rusty nails soaking in benzene. Selenophenol is one of the worst smelling chemicals I have encountered. Thiophenol makes you hold your breath - selenophenol makes you retch.

2. A Buick will kill cancer cells in a Petri dish, but the dosage of Buick in a real patient is probably not feasible.

Permalink to Comment

25. anchor on May 7, 2012 8:41 AM writes...

What is next? A corresponding "Telluride" analog?

Permalink to Comment

26. Cabron on May 7, 2012 3:41 PM writes...

Look at where the work was done, guess the journal had a lack of submissions that month. So are we supposed to take this seriously?

Permalink to Comment

27. Secondaire on May 7, 2012 10:57 PM writes...

What in the...?

I had thoughts about J. Med. Chem jumping the shark before, then disabused myself of them, and now I'm right back there again.

I'd bet these compounds would be cooler with more nitro groups. And maybe an epoxide. Alpha to a guanidine, for good measure!

Permalink to Comment

28. eugene on May 8, 2012 4:21 AM writes...

In the words of Stephen Colbert: the authors had some big, whatever the Mexican word is for cajones, when submitting this one to J. Med. Chem.

Permalink to Comment


Remember Me?


Email this entry to:

Your email address:

Message (optional):

The Last Post
The GSK Layoffs Continue, By Proxy
The Move is Nigh
Another Alzheimer's IPO
Cutbacks at C&E News
Sanofi Pays to Get Back Into Oncology
An Irresponsible Statement About Curing Cancer
Oliver Sacks on Turning Back to Chemistry