新型抗疟和具有细胞毒性的4-橙花叔基儿茶酚衍生物。

New antimalarial and cytotoxic 4-nerolidylcatechol derivatives.

作者信息

Pinto Ana Cristina da Silva, Silva Luis Francisco Rocha, Cavalcanti Bruno Coelho, Melo Márcia Rúbia Silva, Chaves Francisco Célio Maia, Lotufo Letícia Vera Costa, de Moraes Manoel Odorico, de Andrade-Neto Valter Ferreira, Tadei Wanderli Pedro, Pessoa Claudia O, Vieira Pedro Paulo Ribeiro, Pohlit Adrian Martin

机构信息

Universidade Federal do Amazonas, Campus Universitário, 69077-000 Manaus, AM, Brazil.

出版信息

Eur J Med Chem. 2009 Jun;44(6):2731-5. doi: 10.1016/j.ejmech.2008.10.025. Epub 2008 Oct 31.

DOI:10.1016/j.ejmech.2008.10.025

PMID:19084293

Abstract

4-Nerolidylcatechol (1) was isolated from cultivated Pothomorphe peltata root on a multigram scale using straight-forward solvent extraction-column chromatography. New semi-synthetic derivatives of 1 were prepared and tested in vitro against multidrug-resistant Plasmodium falciparum K1 strain. Mono-O-methyl, mono-O-benzyl, O,O-dibenzyl and O,O-dibenzoyl derivatives 2-8 exhibited IC(50) in the 0.67-22.52 microM range. Mono-O-methyl ethers 6 and 7 inhibited the in vitro growth of human tumor cell lines HCT-8 (colon carcinoma), SF-295 (central nervous system), LH-60 (human myeloblastic leukemia) and MDA/MB-435 (melanoma). In general, derivatives 2-8 are more stable to light, air and pH at ambient temperatures than their labile, natural precursor 1. These derivatives provide leads for the development of a novel class of antimalarial drugs with enhanced chemical and pharmacological properties.

摘要

采用简单的溶剂萃取 - 柱色谱法，从人工栽培的盾叶豆薯根中以多克规模分离得到了4 - 橙花叔基儿茶酚（1）。制备了1的新型半合成衍生物，并对其进行体外抗多药耐药恶性疟原虫K1株的测试。单 - O - 甲基、单 - O - 苄基、O,O - 二苄基和O,O - 二苯甲酰基衍生物2 - 8的半数抑制浓度（IC₅₀）在0.67 - 22.52微摩尔范围内。单 - O - 甲基醚6和7抑制人肿瘤细胞系HCT - 8（结肠癌）、SF - 295（中枢神经系统）、LH - 60（人髓性白血病）和MDA/MB - 435（黑色素瘤）的体外生长。一般来说，与不稳定的天然前体1相比，衍生物2 - 8在环境温度下对光、空气和pH更稳定。这些衍生物为开发一类具有增强化学和药理性质的新型抗疟药物提供了线索。