Calicheamicins

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Calicheamicins are a group of structurally very closely related, highly toxic cell toxins . They are 1000 times more potent than adriamycin . These bacterial toxins are produced by the bacterium Micromonospora echinospora . Ingestion of a few grams inevitably leads to death, antidotes are not known. In a correspondingly diluted form, the substance is used in targeted cancer therapy .

properties

The family of calicheamicins includes various structurally closely related chemical compounds. They are structurally, to their biological effect and its mechanism of action esperamicins very similar and also included alongside the enediyne a Allyltrisulfideinheit and seated at the bridgehead enone functionality . Their structures were developed by LEE et al. Published in 1987 and corrected in 1989. The best-known representative is calicheamicin γ1 I , which can now also be produced synthetically.

Examples of calicheamicins
Name (s) Endyne -
substructure 		R = CAS -
number 		PubChem Molecular formula Molar
mass
  • Calicheamicin α1
  • Calicheamicin alpha 1
 Calicheamicin Endiinteil cis (2RS) .svg Calicheamicin glycoside part alpha1 I.svg 44307061 C 48 H 62 IN 3 O 17 S 4 1208.18 g mol −1
  • Calicheamicin β1 (Br)
  • Calicheamicin beta 1 (Br)
 Calicheamicin Glycosidteil beta 1 Br.svg 44307057 C 56 H 76 BrN 3 O 21 S 4 1335.37 g mol −1
  • Calicheamicin γ1 (Br)
  • Calicheamicin gamma 1 (Br)
 Calicheamicin glycoside part gamma (1) Br.svg 44307331 C 55 H 74 BrN 3 O 21 S 4 1321.35 g mol −1
  • Calicheamicin δ1 (I)
  • Calicheamicin delta 1 (I)
 Calicheamicin glycoside part delta1 I.svg 44307145 C 54 H 72 IN 3 O 21 S 4 1354.32 g mol −1
  • Calicheamicin α2
  • Calicheamicin alpha 2
 Calicheamicin Endiinteil cis (2S) .svg Calicheamicin glycoside part alpha2.svg 103716-12-7 6450514 C 48 H 62 IN 3 O 17 S 4 1208.18 g mol −1
  • Calicheamicin α3
  • Calicheamicin alpha 3
 Calicheamicin glycoside part alpha3.svg 103716-13-8 6450515 C 47 H 59 IN 2 O 19 S 4 1211.14 g mol −1
  • Calicheamicin γ1
  • Calicheamicin gamma 1
 Calicheamicin enediin part trans (2S, 9S) Calicheamicin glycoside part gamma (1) .svg 108212-75-5 6438329 C 56 H 78 IN 3 O 21 S 4 1384.39 g mol −1
  • Calicheamicin T
 Calicheamicin glycoside part T.svg 142518-72-7 6449957 C 32 H 43 N 3 O 11 S 3 741.89 g mol −1
  • Calicheamicin γ1 (I)
  • Calicheamicin gamma 1 (I)
 Calicheamicin endiin part trans (9R) .svg Calicheamicin glycoside part gamma (1) I.svg 10486648 C 55 H 74 IN 3 O 21 S 4 1368.35 g mol −1
  • Calicheamicin θ1
  • Calicheamicin theta 1
 Calicheamicin endi component theta1.svg Calicheamicin glycoside part theta 1.svg 44403705 C 57 H 78 IN 3 O 22 S 2 1348.27 g mol −1
  • Calicheamicin ε
  • Calicheamicin epsilon
 Calicheamicin epsilon Tetracyclus.svg Calicheamicin glycoside part epsilon.svg 128050-91-9 5488030 C 54 H 74 IN 3 O 21 S 2 1292.21 g mol −1

effect

Calicheamicins carry an enediyne structural unit that is known to enter into Bergman cyclizations and the resulting diradicals lead to a double-strand break in the DNA . Such a mechanism of action is also being discussed for the calicheamicins.

mythology

The Greek poet Hesiod describes: According to legend, the gods who violated the laws of Olympus had to drink the water of the Styx from a golden goblet . It is believed that the rocks under the Mavronero River , which was associated with Styx, were densely populated with Micromonospora echinospora , so that the amount of dissolved calicheamicin from one cup was sufficient to be fatal.

history

Allegedly Alexander the Great was killed by a goblet of Styx water. The historians say that he suffered severe pain and an insatiable thirst before he died after a week. This is consistent with the symptoms of calicheamicin poisoning. The Greek historian Pausanias writes that goats who accidentally drank the water of the Styx fell dead a short time later for no apparent reason.

Individual evidence

  1. ^ Theodor Dingermann: Pharmaceutical Biology. Springer, 2002, ISBN 978-3-540-42844-2 , p. 231 ( limited preview in Google book search).
  2. ↑ Nicolaou KC, Chen JS, Dalby SM: From nature to the laboratory and into the clinic . In: Bioorganic & Medicinal Chemistry . 17, No. 6, March 2009, pp. 2290-2303. PMID 19028103 . PMC 2665039 (free full text).
  3. ^ MD Lee, JK Manning, DR Williams, NA Kuck, RT Testa, DB Borders: Calicheamicins, a novel family of antitumor antibiotics. 3. Isolation, purification and characterization of calicheamicins beta 1Br, gamma 1Br, alpha 2I, alpha 3I, beta 1I, gamma 1I and delta 1I. In: The Journal of antibiotics . Volume 42, Number 7, July 1989, pp. 1070-1087, PMID 2753814 .
  4. ↑ Folkert Boße: Studies on the Synthesis of New Dynemicin Analogues (PDF; 737 kB)
  5. ↑ S. Walker; R. Landovitz; WD thing; GA Ellestad; D. Kahne: Cleavage behavior of calicheamicin γ1 and calicheamicin T . In: Proc Natl Acad Sci USA . 89, No. 10, 1992, pp. 4608-4612. doi : 10.1073 / pnas.89.10.4608 . PMID 1584797 . PMC 49132 (free full text).
  6. ↑ Angelika Franz: Archeology: Week of torments. In: Spiegel Online . August 2, 2010, accessed July 29, 2016 .
  7. ↑ Alexander the Great poisoned by the River Styx . August 4, 2010. Retrieved August 8, 2010.