Synthesis of novel 3-(aryl)benzothieno[2,3-c]pyran-1-ones from Sonogashira products and intramolecular cyclization: Antitumoral activity evaluation

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Maria Joao R P Queiroz (Author) Other; Ricardo C Calhelha (Author) Other; Luis A Vale Silva (Author) Other; Eugenia Pinto (Author) FFUP; Sao Jose Nascimento, MSJ (Author) FFUP

Journal

Title: European Journal of Medicinal Chemistry

Vol. 44 No. 5

Pages: 1893-1899

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 41 Citations

ISI Web of Science

Scopus - 42 Citations

Scientific classification

CORDIS: Health sciences > Pharmacological sciences > Pharmacy

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-KBC

DOI: 10.1016/j.ejmech.2008.11.002

Resumo (PT): 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 GI50 values in the μM 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. <br> <br> Keywords: Benzo[b]thiophenes; Sonogashira coupling; Intramolecular lactonization; Benzothieno[2,3-c]pyran-1-ones; Antitumor activity <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VKY-4TX78XN-1&_user=2460038&_coverDate=05%2F31%2F2009&_rdoc=11&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%236135%232009%23999559994%23998072%23FLA%23display%23Volume)&_cdi=6135&_sort=d&_docanchor=&_ct=68&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=69161c6e0fcf5ce806d91513e0ba09ca&searchtype=a "> Texto integral </a>

Abstract (EN): 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 mu M 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7