Naturalproductman’s Blog

Hey, is that a natural product?!

Archive for the ‘Cancer’ Category

Enhancing water solubility of a drug (triptolide)

Posted by naturalproductman on November 25, 2015

Gunda Georg and co-workers at the University of Minnesota reported in the Journal of Medicinal Chemistry on the addition of a phosphonooxymethyl group onto triptolide to increase its water solubility by greater than 3,580 times. (slight mistake: Scheme 2 in the paper has the use of benzoyl peroxide shown as “Bn2O2” when it should be “Bz2O2” – Bn2O2 would be benzyl peroxide). Another interesting point from this paper is that this natural product has multiple modes of action where it can covalently attach to proteins (XPB, xeroderma pigmentosum B) or non-covalently (DCTPP1, dCTP pyrophosphatase). Other modified attempts to form soluble prodrugs of this natural product (e.g. carboxylic acid, amino acid esters) resulted in difficult removal of the prodrug group.

11.25.2015 Naturalproductman

J. Med. Chem. paper

Posted in Alzheimer's, Cancer, Diterpene, Epoxides, Medicinal Chemistry, Prodrug | Leave a Comment »

Asperchalasine A

Posted by naturalproductman on September 3, 2015

Here’s a natural product isolation paper that was published in ACIE. Yonghui Zhang and co-workers report on the isolation of asperchalasine A, which induced G-1 phase cell cycle arrest by reducing the expression of cyclin A, CDK2, and CDK6 in cancer cells but not in normal cells at 20 micromolar (pretty high concentration so not so potent in my opinion).

asperchalasine A

ACIE paper

Posted in Cancer, Chemical Biology, Dimer, Terpenoids | Leave a Comment »

Nannocystin A

Posted by naturalproductman on July 17, 2015

Dominic Hoepfner and co-workers from Novartis have reported in ACIE on nannocystin A, which had similar binding properties with didemin B on EF-1alpha (elongation factor 1 inhibitor).

nannocystin A

ACIE paper

Mark Brönstrup and co-workers at Helmholtz Zentrum für Infektionsforschung also reported on the isolation of this small molecule. I wonder if there’s a relationship between the two studies.

ACIE paper

the novartis paper states that their study parallels the work in helmholtz. I guess the two studies just coincidentally resulted in the isolation of the same compound.

Posted in Biosynthesis, Cancer, Chemical Biology, Macrocycles, Macrolides, Peptides | Leave a Comment »

Something to scratch your head about…

Posted by naturalproductman on March 25, 2015

Here’s a weird one from Joseph Ready’s lab at UT Southwestern. Nigricanoside was isolated and reported in JACS in 2007 and was reported to be very biologically active against human breast cancer MCF-7 cells with an IC50 of 3 nM. The research lab had synthesized the molecule and found no biological activity at all, but I looked for the data on biological activity in the supporting information and did not see anything with the biological testing data. Since the strong claim of the lack of activity would make the original isolation paper not as interesting (afterall, most people are mainly interested in the biological activity of natural products besides the exotic structures in the perspective of a synthetic chemist), it would probably have been good for the group to make that data available in their publication. But a counter argument is what is so exciting about negative data? The original isolation paper in JACS has an image on mitotic arrest of breast cancer cells (Figure 2). The biological testing is mentioned in the acknowledgments of the Chemical Science paper with the names of people from two schools.

Another example of this kind of difference in biological activity between a synthesized natural product vs. the original isolation report is with berkelic acid isolated by Andrea Stierle and co-workers from an abandoned copper mine. Barry Snider’s lab had synthesized this polyketide and found no biological activity – the biological data from the NCI screen panel was reported in the supporting information (pages 23-25 in SI) of the JOC paper (Snider group).

Chemical Science paper

Posted in Cancer, Total Synthesis | Leave a Comment »

Dicarabrones A and B

Posted by naturalproductman on March 21, 2015

Yang Ye and co-workers from the Chinese Academy of Sciences have reported in Organic Letters on isolation of dicarabrones A and B.


OL paper

Posted in Cancer, Lactones, Sesquiterpenes | Leave a Comment »

Monamphilectines B and C

Posted by naturalproductman on January 18, 2015

Abimael Rodriguez and co-workers from the University of Puerto Rico have reported in Tetrahedron on the isolation of monamphilectines B and C.


Tetrahedron paper

Posted in Alkaloids, Cancer | Leave a Comment »

Apoptolidins localize in mitochondria

Posted by naturalproductman on November 28, 2014

Gary Sulikowski and co-workers at Vanderbilt University have reported in ACIE on the use of some fluorescent probe versions of apoptolidin natural products and determined that the natural product localizes in the mitochondria of cancer cells.


ACIE paper

Posted in Cancer, Chemical Biology, lung, Polyketides | Leave a Comment »

Plakinamines N and O

Posted by naturalproductman on November 4, 2014

Kirk Gustafson and co-workers from the NCI have reported in JNP on the isolation of plakinamines N and O.

JNP paper

Posted in Alkaloids, Cancer, colon, Steroids | Leave a Comment »

Leiodermatolide synthesis

Posted by naturalproductman on October 28, 2014

Furstner and colleagues have reported in JACS on the synthesis of leiodermatolide.


JACS paper

Posted in Cancer, P-glycoprotein, Protein Targets, Total Synthesis | Leave a Comment »

PPARγ is the target of ainsliatrimer A

Posted by naturalproductman on October 4, 2014

Xiaoguang Lei and co-workers from NIBS have reported in ACIE on the target of ainsliatrimer A, which was determined to be PPARγ.

ainsliatrimer A

ACIE paper

Posted in Cancer, Chemical Biology | Leave a Comment »


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