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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimalarials / chemical synthesis
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Antimalarials / chemistry
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Antimalarials / pharmacology*
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Antimalarials / toxicity
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Antineoplastic Agents, Phytogenic / chemical synthesis
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antineoplastic Agents, Phytogenic / toxicity
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Catechols / chemical synthesis
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Catechols / chemistry
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Catechols / pharmacology*
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Catechols / toxicity
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Resistance
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Drug Screening Assays, Antitumor
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HL-60 Cells
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Humans
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Molecular Structure
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Parasitic Sensitivity Tests
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Piperaceae / chemistry
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Plant Extracts / chemical synthesis
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Plant Extracts / toxicity
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Plant Roots / chemistry
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Plasmodium falciparum / drug effects*
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Stereoisomerism
Substances
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4-nerolidylcatechol
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Antimalarials
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Antineoplastic Agents, Phytogenic
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Catechols
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Plant Extracts