New antimalarial and cytotoxic 4-nerolidylcatechol derivatives

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• 作者：Ana Cristina da Silva Pinto ; Luis Francisco Rocha Silva ; Bruno Coelho Cavalcanti ; Má ; rcia Rú ; bia Silva Melo ; Francisco Cé ; lio Maia Chaves ; Letí ; cia Vera Costa Lotufo ; Manoel Odorico de Moraes ; Valter Ferreira de Andrade-Neto ; W ; erli Pedro Tadei ; Claudia O. Pessoa ; Pedro Paulo Ribeiro
• 关键词：Plasmodium falciparum ; Human colon carcinoma ; Human nervous system cancer ; Melanoma ; Human myeloblastic leukemia ; Semi-synthetic 4-nerolidylcatechol derivatives
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：44
• 期：6
• 页码：2731-2735
• 全文大小：153 K

文摘

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 IC₅₀ in the 0.67–22.52 μM 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.