title: New antimalarial and cytotoxic 4-nerolidylcatechol derivatives.
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.
authors.affiliation: Universidade Federal do Amazonas, Campus Universitário, 69077-000 Manaus, AM, Brazil.
authors.forename: Ana Cristina da Silva
authors.initials: AC
authors.lastname: Pinto
authors.forename: Luis Francisco Rocha
authors.initials: LF
authors.lastname: Silva
authors.forename: Bruno Coelho
authors.initials: BC
authors.lastname: Cavalcanti
authors.forename: Márcia Rúbia Silva
authors.initials: MR
authors.lastname: Melo
authors.forename: Francisco Célio Maia
authors.initials: FC
authors.lastname: Chaves
authors.forename: Letícia Vera Costa
authors.initials: LV
authors.lastname: Lotufo
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Valter Ferreira
authors.initials: VF
authors.lastname: de Andrade-Neto
authors.forename: Wanderli Pedro
authors.initials: WP
authors.lastname: Tadei
authors.forename: Claudia O
authors.initials: CO
authors.lastname: Pessoa
authors.forename: Pedro Paulo Ribeiro
authors.initials: PP
authors.lastname: Vieira
authors.forename: Adrian Martin
authors.initials: AM
authors.lastname: Pohlit
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D026321:Piperaceae / Q000737:chemistry; D010936:Plant Extracts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018517:Plant Roots / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: C110583:4-nerolidylcatechol; D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D010936:Plant Extracts