An expeditious, multi-gram isolation protocol for the ultrapotent SERCA inhibitor thapsigargin

Natural Product Communications

Volumn 2, Issue 6, 2007, Pages 637-642

  Pagani, Alberto ^a,b   Pollastro, Federica ^a,b   Spera, Silvia ^c   Ballero, Mauro ^b   Sterner, Olov ^d   Appendino, Giovanni ^a,b  

^a UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^b Consorzio per lo Studio dei Metaboliti Secondari ^*  (Italy)

^c ENI S P A   (Italy)

^d LUND UNIVERSITY   (Sweden)

Author keywords

Neohelmanthicin D; Serca; Thapsia garganica; Thapsigargicin; Thapsigargin; Thapsivillosin J

Indexed keywords

EID: 78549265885     PISSN: 1934578X     EISSN: 15559475     Source Type: Journal    
DOI: 10.1177/1934578x0700200604     Document Type: Article

References (16)

1. For reviews, see: (a) Avato P. (1997) The genus Thapsia as a source of bioactive compounds, in Virtual Activity, Real Pharmacology (Verotta L. Ed.), Research Signpost, Trivandrum, p. 17-31;.
2. (b) Bhari LE, Makhlouf M. (2001) Thapsia garganica L: A poisonous plant of North Africa. Veterinarian and Human Toxicology, 43, 216-218.
3. For a review, see: Christensen SB, Andersen A, Smitt UW (1997) Sesquiterpenoids from Thapsia species and medicinal chemistry of the thapsigargins. Progress in the Chemistry of Organic Natural Products, 71, 129-167.
4. For a recent review, see: Toyoshima C, Incsi G. (2004) Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum. Annual Review Biochemistry, 73, 269-292.
5. Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE, Christensen SB. (2001) Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells. Journal of Medicinal Chemistry, 44, 4696-4703.
6. Liu H, Jensen KG, Trail LM, Chen M, Zhai L, Olsen CE, Sohoel H, Denmeade SR, Isaacs JT, Christensen SB (2006) Cytotoxic phcnylpropanoids and an aditional thapsigargin analogue isolated from Thapsia gaigahica. Phytochemistry, 67, 2651-2658.
7. Barrett AGM, Smith ML, Zecri FJ (1998) Impurity annihilation; a strategy for solution phase combinatorial chemistry with minimal purification. Chemical Communications, 2317-2318.
8. Smitt UW, Moldt P, Christensen SB (1986) Structure of a pro 1, 4-dimethylazulene guaianolide from Thapsia garganica L. Acta Che mica Scandinava, 45, 56-61.
9. (a) Isolation: Smitt UW, Christensen SB. (1991) Nortrilobolide, a new potent guaianolide segretagogue from Thapsia garganica. Planta Medica, 57, 196-197;.
10. (b) Total synthesis: Ley SV, Antonello A, Balkus EP, Booth DT, Christensen SB, Cleator E, Gold H, Hogenauer K, Hunger U, Myers RM, Oliver SF, Simic O, Smith MD, Seihoel H, Woolford AJA. (2004) Synthesis of the thapsigargins. Proceedings of the National Academy of Sciences USA, 101, 12073-12078.
11. Nortrilobolide shows SERCA-inhibiting properties very similar to those of thapsigargin, and has been successfully employed for the synthesis of second-generation SERCA inhibitors to target prostate cancer cells (Søhoel H, Jensen AML, Moller JV, Nissen P, Denmeade SR, Isaacs JT, Olsen CE, Christensen SB (2006) Natural products as starting material for development of second- generation SERCA inhibitors targeted towards prostate cancer cells. Bioorganic & Medicinal Chemistry, 14, 2810-2815).
12. 2+pump inhibitor thapsigargin. Acta Chemica Scandinava, 48, 340-346.
13. Jager AK, Gudiksen L, Adsersen A, Smitt UW. (1993) High-performance liquid chromatography of thapsigargins. Journal of Chromatography, 634, 135-137.
14. Christensen SB, Norup E, Rasmussen U, Ogaard Madsen J. (1984) Structure of histamine releasing guaianolides from Thapsia garganica. Phytochemistry, 23, 1659-1663.
15. Supplied by Alexis Biochemicals.
16. Ester acid names: Ang = Angelic acid; But = n-Butanoic acid; Hex = n-Hexanoic acid; Oct = n-Octanoic acid; Dec = n-Decanoic acid; Val = 3-Methylbutyric (isovalerianic) acid.