Synthesis of novel 3-(aryl)benzothieno[2,3-c]pyran-1-ones from Sonogashira products and intramolecular cyclization: Antitumoral activity evaluation.
Several novel 3-(aryl)benzothieno[2,3-c]pyran-1-ones (tricyclic lactones) were prepared either by a tandem one-pot Sonogashira coupling and intramolecular cyclization, reacting the 3-bromobenzo[b]thiophene-2-carboxylic acid with arylacetylenes, or by Sonogashira coupling of the methyl 3-bromobenzo[b]thiophene-2-carboxylate or the methyl 3-bromo-6-methoxybenzo[b]thiophene-2-carboxylate with arylacetylenes followed by an electrophilic intramolecular cyclization using iodine or TFA in two separate steps. The Sonogashira products and the tricyclic lactones obtained were evaluated for their capacity to inhibit the in vitro growth of three human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). Most of the compounds showed a high growth inhibitory effect on all the tested cell lines, with GI(50) values in the muM range. A structure-activity relationship was established for the Sonogashira products and for the tricyclic lactones, namely related to the presence and position of substituents (OMe and/or F) in the benzothiophene moiety or in the phenyl ring.
Queiroz
Maria-João R P
MJ
Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Calhelha
Ricardo C
RC
Vale-Silva
Luís A
LA
Pinto
Eugénia
E
São-José Nascimento
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes
D000970:Antineoplastic Agents; D011714:Pyrans; D013876:Thiophenes; C088015:benzothiophene