Design, synthesis and anticancer activities of stilbene-coumarin hybrid compounds: Identification of novel proapoptotic agents.
The naturally occurring coumarins and resveratrol, attract great attention due to their wide range of biological properties, including anticancer, antileukemic, antibacterial and anti-inflammatory activities; moreover, their cancer chemopreventive property have been recently emphasized. A novel class of hybrid compounds, obtained by introducing a substituted trans-vinylbenzene moiety on a coumarin backbone, was synthesized and evaluated for the antitumor profile. A number of derivatives showed a good antiproliferative activity, in some cases higher to that of the reference compound resveratrol. The most promising compounds in this series were 14 and 17, endowed with excellent antiproliferative and proapoptotic activities. The present study suggests that the 7-methoxycoumarin nucleus, together with the 3,5-disubstitution pattern of the trans-vinylbenzene moiety, are likely promising structural features to obtain excellent antitumor compounds endowed with a apoptosis-inducing capability.
Belluti
Federica
F
Dipartimento di Scienze Farmaceutiche, Via Belmeloro, 6, I-40126 Bologna, Italy. federica.belluti@unibo.it
Fontana
Gabriele
G
Dal Bo
Laura
L
Carenini
Nives
N
Giommarelli
Chiara
C
Zunino
Franco
F
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002678:Chimera; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010087:Oxides / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D003374:Coumarins; D010087:Oxides; D013267:Stilbenes; D000077185:Resveratrol