Demecolcine

Demecolcine

Systematic (IUPAC) name
(S)-1,2,3,10-Tetramethoxy-7-methylamino-6,7-dihydro-5H-benzo[a]heptalen-9-one
Identifiers
CAS Number	477-30-5 Y
ATC code	L01CC01 (WHO)
PubChem	CID: 2832
ChemSpider	191135 Y
UNII	Z01IVE25KI Y
ChEMBL	CHEMBL312862 Y
Chemical data
Formula	C21H25NO5
Molecular mass	371.43 g/mol
SMILES O=C/1C(\OC)=C/C=C2\C(=C\1)[C@@H](NC)CCc3c2c(OC)c(OC)c(OC)c3
InChI InChI=1S/C21H25NO5/c1-22-15-8-6-12-10-18(25-3)20(26-4)21(27-5)19(12)13-7-9-17(24-2)16(23)11-14(13)15/h7,9-11,15,22H,6,8H2,1-5H3/t15-/m0/s1 Y Key:NNJPGOLRFBJNIW-HNNXBMFYSA-N Y
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Demecolcine, also known as Colcemid, is a drug used in chemotherapy. It is closely related to the natural alkaloid colchicine with the replacement of the acetyl group on the amino moiety with methyl, but it is less toxic. It depolymerises microtubules and limits microtubule formation (inactivates spindle fibre formation), thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.

During cell division, demecolcine inhibits mitosis at metaphase by inhibiting spindle formation. Medically, demecolcine has been used to improve the results of cancer radiotherapy by synchronising tumour cells at metaphase, the radiosensitive stage of the cell cycle.

In animal cloning procedures, demecolcine makes an ovum eject its nucleus, creating space for insertion of a new nucleus.

Mechanism of action

Demecolcine is a microtubule-depolymerizing drug like vinblastine. It acts by two distinct mechanisms. At very low concentration it binds to microtubule plus end to suppress microtubule dynamics. Recent study has found at higher concentration Colcemid can promote microtubule detachment from microtubule organizing center. Detached microtubules with unprotected minus end depolymerizes with time. Cytotoxicity of the cells seems to correlate better with microtubule detachment. Lower concentration affects microtubule dynamics and cell migration.