Two new bromoindole alkaloids have been isolated from the ethanolic extract of the red alga Laurencia similis. On the basis of chemical and spectroscopic methods （including 1D and 2D NMR technique）, their structures have been elucidated as 2,2＇,5,5＇,6,6＇- sixibromo-3, 3＇-bi-lH-indole and 3, 5-dibromo-1-methylindole, respectively.
Hua SuZhao Hui YuanJing LiShu Ju GuoLi Ping DengLi Jun HanXiao Bin ZhuDa Yong Shi
To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-（2,3-dibromo-4,5-dihydroxybenzyl）-2,3-dibromo-4,5-dihydroxy benzyl methyl ether （1）, （＋）-3-（2,3-dibromo-4,5-dihydroxyphenyl）-4-bromo-5,6-dihydroxy-1,3- dihydroisobenzofuran （2）, 3-bromo-4-（2,3-dibromo-4,5-dihydroxybenzyl）-5-methoxymethyl-pyrocatechol （3）, 2,2＇,3,3＇-tetrabromo-4,4＇,5,5＇-tetrahydroxy-diphenylmethane （4）, bis（2,3-dibromo-4,5-dihydroxybenzyl） ether （5）, 2,2＇,3-tribromo-3＇,4,4＇,5-tetrahydroxy-6＇-ethyloxymethyldiphenylmethane （6） were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTF assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Be17402 and HCT-8. Their inhibitory activity against protein tyrosine kinase （PTK） with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana （EELN） was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 pg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4% respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.
