Anthracycline

Doxorubicin as an intercalating agent. Two doxorubicin molecules intercalated within DNA.[1]

Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from Streptomyces peucetius bacterium.[2][3][4] These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cancer, and lung cancers. The first anthracycline discovered was daunorubicin (trade name Daunomycin), which is produced naturally by Streptomyces peucetius, a species of Actinomycetota. Clinically the most important anthracyclines are doxorubicin, daunorubicin, epirubicin and idarubicin.[5]

The anthracyclines are among the most effective anticancer treatments ever developed and are effective against more types of cancer than any other class of chemotherapeutic agents.[5][6][7] Their main adverse effect is cardiotoxicity, which considerably limits their usefulness. Use of anthracyclines has also been shown to be significantly associated with cycle 1 severe or febrile neutropenia.[8] Other adverse effects include vomiting.

The drugs act mainly by intercalating with DNA and interfering with DNA metabolism and RNA production. Cytotoxicity is primarily due to inhibition of topoisomerase II after the enzyme induces a break in DNA, preventing religation of the break and leading to cell death. The basic structure of anthracyclines is that of a tetracyclic molecule with an anthraquinone backbone connected to a sugar moiety by a glycosidic linkage. When taken up by a cell the four ring structure intercalates between DNA bases pairs while the sugar sits within the minor groove and interacts with adjacent base pairs.

  1. ^ Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH (March 1990). "Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin". Biochemistry. 29 (10): 2538–49. doi:10.1021/bi00462a016. PMID 2334681.
  2. ^ Trevor AJ, Katzung BG, Masters SB, Kruidering-Hall M (2010). "Chapter 54: Cancer Chemotherapy: Anthracycline Antibiotics". Pharmacology Examination & Board Review. New York: McGraw-Hill Medical.
  3. ^ Fujiwara A, Hoshino T, Westley J (1985). "Anthracycline Antibiotics". Critical Reviews in Biotechnology. 3 (2): 133–157. doi:10.3109/07388558509150782.
  4. ^ Cite error: The named reference McGowan_2017 was invoked but never defined (see the help page).
  5. ^ a b Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology. 19 (6): 670–86. PMID 1462166.
  6. ^ Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (June 2004). "Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity". Pharmacological Reviews. 56 (2): 185–229. doi:10.1124/pr.56.2.6. PMID 15169927. S2CID 13138853.
  7. ^ Peng X, Chen B, Lim CC, Sawyer DB (June 2005). "The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine". Molecular Interventions. 5 (3): 163–71. doi:10.1124/mi.5.3.6. PMID 15994456.
  8. ^ Lyman GH, Kuderer NM, Crawford J, Wolff DA, Culakova E, Poniewierski MS, Dale DC (May 2011). "Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy". Cancer. 117 (9): 1917–27. doi:10.1002/cncr.25691. PMC 3640637. PMID 21509769.