Rebeccamycin

Rebeccamycin (NSC 655649) is a weak topoisomerase I inhibitor isolated from Nocardia sp. It is structurally similar to staurosporine, but does not show any inhibitory activity against protein kinases. It shows significant antitumor properties in vitro (IC50=480nM against mouse B16 melanoma cells and IC50=500nM against P388 leukemia cells). It is an antineoplastic antibiotic and an intercalating agent.

Rebeccamycin
Clinical data
Other names7,10-dichloro-8-(3,4-dihydroxy-6-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-2-yl)-8,9-dihydro-1H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione
ATC code
  • none
Identifiers
IUPAC name
  • 1,11-dichloro-12-(4-O-methyl-β-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H21Cl2N3O7
Molar mass570.38 g·mol−1
3D model (JSmol)
SMILES
  • CO[C@@H]1[C@H](O[C@H]([C@@H]([C@H]1O)O)N2C3=C(C=CC=C3Cl)C4=C5C(=C6C7=C(C(=CC=C7)Cl)NC6=C42)C(=O)NC5=O)CO
InChI
  • InChI=1S/C27H21Cl2N3O7/c1-38-24-13(8-33)39-27(23(35)22(24)34)32-20-10(5-3-7-12(20)29)15-17-16(25(36)31-26(17)37)14-9-4-2-6-11(28)18(9)30-19(14)21(15)32/h2-7,13,22-24,27,30,33-35H,8H2,1H3,(H,31,36,37)/t13-,22-,23-,24-,27-/m1/s1 Y
  • Key:QEHOIJJIZXRMAN-QZQSLCQPSA-N Y
 NY (what is this?)  (verify)

Becatecarin (BMS-181176) is a synthetic analog of rebeccamycin.[1]

Rebeccamycin and becatecarin have been tested in phase II clinical trials for the treatment of lung cancer, liver cancer, breast cancer, lymphoma, retinoblastoma, kidney cancer, and ovarian cancer.[2]

References
  1. Clinical trial number NCT00006017 at ClinicalTrials.gov
  2. "2 Studies found for: BRN 4732638". Clinical Trials Gov.

Further reading
  • Nettleton DE, Doyle TW, Krishnan B, Matsumoto GK, Clardy J (January 1985). "Isolation and structure of rebeccamycin-a new antitumor antibiotic from Nocardia aerocoligenes". Tetrahedron Letters. 26 (34): 4011–4014. doi:10.1016/S0040-4039(00)89280-1.
  • Bush JA, Long BH, Catino JJ, Bradner WT, Tomita K (May 1987). "Production and biological activity of rebeccamycin, a novel antitumor agent". The Journal of Antibiotics. 40 (5): 668–78. doi:10.7164/antibiotics.40.668. PMID 3112080.
  • Anizon F, Belin L, Moreau P, Sancelme M, Voldoire A, Prudhomme M, et al. (October 1997). "Syntheses and biological activities (topoisomerase inhibition and antitumor and antimicrobial properties) of rebeccamycin analogues bearing modified sugar moieties and substituted on the imide nitrogen with a methyl group". Journal of Medicinal Chemistry. 40 (21): 3456–65. doi:10.1021/jm9702084. PMID 9341921.
  • Bailly C, Riou JF, Colson P, Houssier C, Rodrigues-Pereira E, Prudhomme M (April 1997). "DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin". Biochemistry. 36 (13): 3917–29. doi:10.1021/bi9624898. PMID 9092822.
  • Bailly C, Qu X, Graves DE, Prudhomme M, Chaires JB (May 1999). "Calories from carbohydrates: energetic contribution of the carbohydrate moiety of rebeccamycin to DNA binding and the effect of its orientation on topoisomerase I inhibition". Chemistry & Biology. 6 (5): 277–86. doi:10.1016/S1074-5521(99)80073-8. PMID 10322124.


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