New antimalarial and cytotoxic 4-nerolidylcatechol derivatives.

European journal of medicinal chemistry (2008-12-17)
Ana Cristina da Silva Pinto, Luis Francisco Rocha Silva, Bruno Coelho Cavalcanti, Márcia Rúbia Silva Melo, Francisco Célio Maia Chaves, Letícia Vera Costa Lotufo, Manoel Odorico de Moraes, Valter Ferreira de Andrade-Neto, Wanderli Pedro Tadei, Claudia O Pessoa, Pedro Paulo Ribeiro Vieira, Adrian Martin Pohlit
要旨

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.

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製品内容

Sigma-Aldrich
クロロキン 二リン酸塩, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
1,2-ジヒドロキシベンゼン, ReagentPlus®, ≥99%
Sigma-Aldrich
ピロカテコール, ≥99%
Sigma-Aldrich
キニーネ, suitable for fluorescence, anhydrous, ≥98.0% (dried material, NT)
Sigma-Aldrich
キニーネ, 90%
Sigma-Aldrich
ピロカテコール, suitable for plant cell culture, BioReagent, ≥99%, powder
Sigma-Aldrich
ピロカテコール, purified by sublimation, ≥99.5%