Total Synthesis and Target Identification of the Curcusone Diterpenes

Total synthesis of the actinoallolides and a designed photoaffinity probe for target identification

Organic & Biomolecular Chemistry ◽

10.1039/d0ob01831g ◽

2020 ◽

Vol 18 (40) ◽

pp. 8109-8118

Author(s):

Matthew J. Anketell ◽

Theodore M. Sharrock ◽

Ian Paterson

Keyword(s):

Natural Products ◽

Total Synthesis ◽

Late Stage ◽

Target Identification ◽

Convergent Synthesis

A convergent synthesis of the actinoallolides with late-stage diversification provides access to a photoaffinity probe to identify the target of these potent anti-trypanosomal natural products.

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Synthesis of ramariolide natural products and discovery of their targets in mycobacteria

Chemical Communications ◽

10.1039/c6cc08365j ◽

2017 ◽

Vol 53 (1) ◽

pp. 107-110 ◽

Cited By ~ 15

Author(s):

Johannes Lehmann ◽

Johannes Richers ◽

Alexander Pöthig ◽

Stephan A. Sieber

Keyword(s):

Natural Products ◽

Total Synthesis ◽

Target Identification

The total synthesis of ramariolides A–D and ABPP (photoprobe) derivatives have been synthesized for target identification in mycobacterial strains.

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Total Synthesis, Biological Evaluation, and Target Identification of RareAbiesSesquiterpenoids

Journal of the American Chemical Society ◽

10.1021/jacs.8b07652 ◽

2018 ◽

Vol 140 (50) ◽

pp. 17465-17473 ◽

Cited By ~ 9

Author(s):

Dexter C. Davis ◽

Dominic G. Hoch ◽

Li Wu ◽

Daniel Abegg ◽

Brandon S. Martin ◽

...

Keyword(s):

Total Synthesis ◽

Target Identification ◽

Biological Evaluation

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(+)- and (-)-Itampolin A: First Total Synthesis, Anticancer Effect Through Inhibition of Phospho p38 Expression

Current Organic Synthesis ◽

10.2174/1570179414666170215092631 ◽

2017 ◽

Vol 14 (6) ◽

pp. 912-917

Author(s):

Jingwei Liang ◽

Xinyang Li ◽

Xin He ◽

Qi Sun ◽

Tingjian Zhang ◽

...

Keyword(s):

Western Blot ◽

Total Synthesis ◽

Blot Analysis ◽

Western Blot Analysis ◽

Target Identification ◽

A549 Cells ◽

Marine Sponges ◽

Potential Target ◽

Mtt Method ◽

Biological Tests

Aim and Objective: The brominated tyrosine alkaloids which have broad biological activity are commonly found in marine sponges of the Verongida order, However, with the discovery of itampolin A and B from the Madagascan sponge, Iotrochota purpurea, a plurality of brominated tyrosine derivatives have been found in the sponge Iotrochota purpurea. This study was undertaken to study antitumor activity of itampolin A and to explore the possible mechanism. Material and Method: The total synthesis of itampolin A was first performed to obtain purified brominated tyrosine alkaloid, then the cytotoxicities of itampolin A were evaluated by MTT method against H460 and A549 cells. To explore the possible mechanism, potential target identification by latest integrated pharmacophore matching platform of itampolin A was carried out using PharmMapper Server. Finally, expression of phospho p38α protein was studied using the western blot analysis. Results: Itampolin A and enantiomer of itampolin A were obtained, the latter is a novel compound named (-)- itampolin A, which exhibited significant anticancer activity in the biological tests. After potential target identification by latest integrated pharmacophore matching platform of itampolin A, p38α was screened out as the target protein. Then in the Western-blot analysis, it was proposed that (-)-itampolin A inhibited tumor cells by reducing the phospho-p38α expression. Conclusion: (+)-itampolin A was a brominated tyrosine derivative, isolated from the sponge Iotrochota purpurea. For the first time, the total synthesis of itampolin A was achieved. The enantiomer, (-)-itampolin A was found to show inhibitory activity on the cultured lung cancer A549 cells. The underlying anticancer mechanisms may be associated with its binding to p38α and then decrease in the phospho-p38 expression.

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