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

• Type: Article in International Scientific Journal
• Date: 2008

Authors

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

Journal

Title: Bioorganic and Medicinal Chemistry

Vol. 16

Pages: 5584-5589

ISSN: 0968-0896

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 42 Citations

ISI Web of Science

Scopus - 29 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Health sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6