Cytotoxic epimeric withaphysalins from leaves of Acnistus arborescens.
Phytochemical analysis of the leaves of Acnistus arborescens (Solanaceae) resulted in the isolation of two new epimeric withaphysalins (17S,20R,22R)-5beta,6beta: 18,20-diepoxy-4beta,18-dihydroxy-1-oxowitha-24-enolide (2, 18R and 18S), together with the known withaphysalin F (1, 18R and 18S). Their structures were established by spectroscopic methods, including 2D NMR data and comparison with literature data. Compounds 1 and 2 dis-played potent cytotoxic activities against several cancer cell lines with IC50 values in the range of 0.20 to 1.46 microg/mL for 1 and 0.89 to 8.08 microg/mL for 2. The strong cytotoxicity presented by 1 suggests that in this series of compounds, the 2,3-unsaturated ketone moiety is an important pharmacophoric unit. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation after 24 hours of incubation on leukemic cells.
Veras
Maria Leopoldina
ML
Curso de Pós-Graduação em Química Orgânica, Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidiade Federal do Ceará, Rua Cel Nunes de Melo 1127, 60430-270 Fortaleza, Ceará, Brazil.
Bezerra
Maria Zeneide B
MZ
Braz-Filho
Raimundo
R
Pessoa
Otilia Deusdênia L
OD
Montenegro
Raquel Carvalho
RC
do O Pessoa
Cláudia
C
de Moraes
Manoel Odorico
MO
Costa-Lutufo
Letícia Veras
LV
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D004875:Ergosterol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D019998:Racemases and Epimerases; D012632:Secosteroids / Q000737:chemistry / Q000494:pharmacology*; D019657:Solanaceae
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012632:Secosteroids; C488716:withaphysalin F; D019998:Racemases and Epimerases; D004875:Ergosterol