Camptothecin

Camptothecin
Clinical data
ATC code
  • none
Identifiers
  • (S)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]
    quinoline-3,14-(4H,12H)-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.113.172 Edit this at Wikidata
Chemical and physical data
FormulaC20H16N2O4
Molar mass348.358 g·mol−1
3D model (JSmol)
Melting point275 to 277 °C (527 to 531 °F)
  • O=C\1N4\C(=C/C2=C/1COC(=O)[C@]2(O)CC)c3nc5c(cc3C4)cccc5
  • InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1 checkY
  • Key:VSJKWCGYPAHWDS-FQEVSTJZSA-N checkY
  (verify)

Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native to China used in traditional Chinese medicine.[1][2] It has been used clinically in China for the treatment of gastrointestinal tumors.[3] CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers.[4] However, it has low solubility and adverse effects have been reported when used therapeutically,[3] so synthetic and medicinal chemists have developed numerous syntheses of camptothecin[5][6][7] and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy[8] today: topotecan, irinotecan, belotecan, and trastuzumab deruxtecan.[9][10] Camptothecin has also been found in other plants including Chonemorpha fragrans.[11]

  1. ^ Govindachari TR, Viswnathan N (1972). "the stem bark of Mappia foetida, a tree native to India, has proved to be another source significant for the isolation of camptothecin". Phytochemistry. 11 (12): 3529–31. doi:10.1016/s0031-9422(00)89852-0.
  2. ^ Efferth T, Fu YJ, Zu YG, Schwarz G, Konkimalla VS, Wink M (2007). "Molecular target-guided tumor therapy with natural products derived from traditional Chinese medicine". Current Medicinal Chemistry. 14 (19): 2024–2032. doi:10.2174/092986707781368441. PMID 17691944.
  3. ^ a b "Camptothecin". Chemnetbase - Dictionary of Drugs.
  4. ^ Wang XH, Huang M, Zhao CK, Li C, Xu L (June 2019). "Design, synthesis, and biological activity evaluation of campthothecin-HAA-Norcantharidin conjugates as antitumor agents in vitro". Chemical Biology & Drug Design. 93 (6): 986–992. doi:10.1111/cbdd.13397. PMID 30218487. S2CID 52277958.
  5. ^ Reich HJ. "Curran Synthesis of Camptothecin". Archived from the original on 2009-09-05.
  6. ^ Reich HJ. "Comins Synthesis of Camptothecin". Archived from the original on 2009-09-05.
  7. ^ Reich HJ. "Rapaport Synthesis of Camptothecin". Archived from the original on September 7, 2009.
  8. ^ Takimoto CH, Calvo E (2008). "Principles of Oncologic Pharmacotherapy". In Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (eds.). Cancer Management: A Multidisciplinary Approach (11th ed.). Archived from the original on 15 May 2009.
  9. ^ Wall ME, Wani MC, Cook CA, Palmer KH, McPhail AA, Sim GA (1966). "Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminate". Journal of the American Chemical Society. 88 (16): 3888–3890. doi:10.1021/ja00968a057.
  10. ^ Samuelsson G (2004). Drugs of Natural Origin: a Textbook of Pharmacognosy (5 ed.). Stokkholm: Swedish pharmaceutical press. ISBN 91-974318-4-2.
  11. ^ Isah T, Umar S (September 2018). "Influencing in vitro clonal propagation of Chonemorpha fragrans (moon) Alston by culture media strength, plant growth regulators, carbon source and photo periodic incubation". Journal of Forestry Research. 31: 27–43. doi:10.1007/s11676-018-0794-3. S2CID 52297102.