Synthesis of new heteroaryl and heteroannulated indoles from dehydrophenylalanines: Antitumor evaluation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Maria Joao R P Queiroz (Autor) Outra; Ana S Abreu (Autor) Outra; Solange S D Carvalho (Autor) Outra; Paula M T Ferreira (Autor) Outra; Nair Nazareth (Autor) Outra; Sao Jose J Nascimento (Autor) FFUP

Revista

Título: Bioorganic and Medicinal Chemistry

Vol. 16

Páginas: 5584-5589

ISSN: 0968-0896

Editora: Elsevier

Indexação

ISI Web of Knowledge - 42 Citações

ISI Web of Science

Scopus - 29 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

CORDIS: Ciências da Saúde

Outras Informações

ID Authenticus: P-003-ZD5

DOI: 10.1016/j.bmc.2008.04.004

Resumo (PT): A 3-(dibenzothien-4-yl)indole and a phenylbenzothienoindole or a 3-(dibenzofur-4-yl)indole and a phenylbenzofuroindole were prepared by a metal-assisted C–N intramolecular cyclization of the methyl esters of N-Boc-(E) or (Z)-β-dibenzothien-4-yl or β-dibenzofur-4-yl dehydrophenylalanines. The latter were obtained by Suzuki cross-coupling of the methyl esters of N-Boc-(E) or (Z)-β-bromodehydrophenylalanines with dibenzothien-4-yl or dibenzofur-4-yl boronic acids, in high yields. The intramolecular cyclization from E or Z pure Suzuki-coupling products gave the corresponding heteroaryl and heteroannulated indoles, in different ratios, by either direct cyclization or cyclization after isomerisation. Three of the cyclized compounds, the two heteroarylindoles and the phenylbenzothienoindole, 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). The methyl 3-(dibenzothien-4-yl)indole-2-carboxylate was the most potent compound with GI50 values ranging from 11 to 17 μM. <br> <br> Keywords: Dehydrophenylalanines; Suzuki-coupling; Metal-assisted C–N intramolecular cyclization; Heteroarylindoles; Heteroannulated indoles; Antitumor evaluation <br> <a target="_blank" href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF8-4S73RC7-4&_user=2460038&_coverDate=05%2F15%2F2008&_rdoc=24&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%235220%232008%23999839989%23690171%23FLA%23display%23Volume)&_cdi=5220&_sort=d&_docanchor=&_ct=48&_acct=C000057398&_version=1&_urlVersion=0&_userid=2460038&md5=3a3ebce137d33cc41436fe80689d5cc3&searchtype=a"> Texto integral</a> <br> <br>

Abstract (EN): A 3-(dibenzothien-4-yl) indole and a phenylbenzothienoindole or a 3-(dibenzofur-4-yl) indole and a phenylbenzofuroindole were prepared by a metal-assisted C-N intramolecular cyclization of the methyl esters of N-Boc-(E)or(Z)-beta-dibenzothien-4-yl or beta-dibenzofur-4-yl dehydrophenylalanines. The latter were obtained by Suzuki cross-coupling of the methyl esters of N-Boc-(E) or (Z)-beta-bromodehydrophenylalanines with dibenzothien-4-yl or dibenzofur-4-yl boronic acids, in high yields. The intramolecular cyclization from E or Z pure Suzuki-coupling products gave the corresponding heteroaryl and heteroannulated indoles, in different ratios, by either direct cyclization or cyclization after isomerisation. Three of the cyclized compounds, the two heteroarylindoles and the phenylbenzothienoindole, 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). The methyl 3-(dibenzothien-4-yl) indole-2-carboxylate was the most potent compound with GI(50) values ranging from 11 to 17 mu M.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6