Design, synthesis, and biological evaluation of thiophene analogues of chalcones.
Chalcones are characterized by possessing an enone moiety between two aromatic rings. A series of chalcone-like agents, in which the double bond of the enone system is embedded within a thiophene ring, were synthesized and evaluated for antiproliferative activity and inhibition of tubulin assembly and colchicine binding to tubulin. The replacement of the double bond with a thiophene maintains antiproliferative activity and therefore must not significantly alter the relative conformation of the two aryl rings. The synthesized compounds were found to inhibit the growth of several cancer cell lines at nanomolar to low micromolar concentrations. In general, all compounds having significant antiproliferative activity inhibited tubulin polymerization with an IC(50)<2microM. Several of these compounds caused K562 cells to arrest in the G2/M phase of the cell cycle.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Carrion
Maria Dora
MD
Cara
Carlota Lopez
CL
Cruz-Lopez
Olga
O
Preti
Delia
D
Tolomeo
Manlio
M
Grimaudo
Stefania
S
Di Cristina
Antonella
A
Zonta
Nicola
N
Balzarini
Jan
J
Brancale
Andrea
A
Sarkar
Taradas
T
Hamel
Ernest
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001921:Brain; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D047188:Chalcones; D013876:Thiophenes; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine