Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds.
J Enzyme Inhib Med Chem
; 19(1): 1-10, 2004 Feb.
Article
in En
| MEDLINE
| ID: mdl-15202487
ABSTRACT
A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Mannich Bases
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
J Enzyme Inhib Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2004
Document type:
Article
Affiliation country:
Canada