Geiparvarin analogues. 4. Synthesis and cytostatic activity of geiparvarin analogues bearing a carbamate moiety or a furocoumarin fragment on the alkenyl side chain.
J Med Chem
; 37(15): 2401-5, 1994 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-8057288
ABSTRACT
As a continuation of previous studies on the synthesis and antitumor activity of geiparvarin analogues bearing a carbamate moiety in the alkyl side chain, a series of N-substituted [(E)-3-(4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl)-2- butenyl]carbamates (15a-f) were synthesized and tested with the objective to investigate the reason for the marked difference of cytostatic activity found between alkyl and phenyl derivatives. A series of compounds, characterized by different physicochemical properties, were designed in order to study this hypothesis. Moreover, to further investigate the modification of the alkenyl side chain, (E)- and (Z)-[2-(4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl)propenyl]-7H-furo[3,2- g][1]benzopyran-7-one (11a,b) were synthesized, the latter compounds being the combination of two units, namely, the 3(2H)-furanone ring system endowed with potent alkylating properties and the furocoumarin portion which binds to DNA resulting in potential DNA-targeted alkylating agents. The compounds were tested for their cytostatic activity against proliferation of murine (L1210) and human (Molt/4, CEM, or MT-4) tumor cells. The highest cytostatic activity found within both series of carbamic derivatives (15a-d,k and 15e,g-j) was associated with the highest global lipophilicity. With regard to compounds 11a,b, the cytostatic activity of (Z)-furocoumarin 11b might be related to a specific interaction with DNA (i.e., intercalation).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Furocumarinas
/
Carbamatos
/
Cumarínicos
/
Antineoplásicos Fitogênicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Itália