Geiparvarin analogues. 2. Synthesis and cytostatic activity of 5-(4-arylbutadienyl)-3(2H)-furanones and of N-substituted 3-(4-oxo-2-furanyl)-2-buten-2-yl carbamates.
In an attempt to determine some of the structural features of geiparvarin (1) that account for its cytostatic activity in vitro, a series of geiparvarin analogues (10a-i, 1, 12, and 14-16) which contain novel modifications in the region of the olefinic double bond and of the coumarin moiety have been designed and synthesized. Among the derivatives containing a carbamate moiety, only the analogues containing a carbamate group linked to an alkyl moiety 10b-i were endowed with potent cytostatic activity, whereas the corresponding benzene derivative 10a was devoid of any antiproliferative activity. 6-Methoxygeiparvarin 101 proved equally effective as geiparvin (1), while compounds containing an additional double bond at the side chain (12 and 14-16) were invariably 5-100-fold less effective than geiparvarin. Diene derivative 15, bearing a coumarin moiety, was essentially inactive against murine (L1210, FM3A) tumor cells but exhibited good activity against human (Molt/4F, MT-4) tumor cells.
Simoni
D
D
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
Manfredini
S
S
Tabrizi
M A
MA
Bazzanini
R
R
Baraldi
P G
PG
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000627:therapeutic use; D002219:Carbamates / Q000138:chemical synthesis* / Q000627:therapeutic use; D003374:Coumarins / Q000627:therapeutic use*; D005663:Furans / Q000138:chemical synthesis* / Q000627:therapeutic use; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D003374:Coumarins; D005663:Furans; C058446:geiparvarin