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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: derekb.lowe@gmail.com Twitter: Dereklowe

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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!

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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


COMMENTS

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

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

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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?

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

Bonus points for testing organometallic compounds.

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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.

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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

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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.

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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).

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

Good lord. Organic compounds from Mars.

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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.

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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.

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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.)

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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.

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

Did the Dinos make these?

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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)

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

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

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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.

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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?

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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.

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

Another "high impact" paper from the "Instituto de Química"... 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.

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

Orally available?

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

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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?

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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.

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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.

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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.

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


What is next? A corresponding "Telluride" analog?

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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?

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

What the...how 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!

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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

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