New antimalarial and cytotoxic 4-nerolidylcatechol derivatives.
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.
Pinto
Ana Cristina da Silva
AC
Universidade Federal do Amazonas, Campus Universitário, 69077-000 Manaus, AM, Brazil.
Silva
Luis Francisco Rocha
LF
Cavalcanti
Bruno Coelho
BC
Melo
Márcia Rúbia Silva
MR
Chaves
Francisco Célio Maia
FC
Lotufo
Letícia Vera Costa
LV
de Moraes
Manoel Odorico
MO
de Andrade-Neto
Valter Ferreira
VF
Tadei
Wanderli Pedro
WP
Pessoa
Claudia O
CO
Vieira
Pedro Paulo Ribeiro
PP
Pohlit
Adrian Martin
AM
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
C110583:4-nerolidylcatechol; D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D010936:Plant Extracts