New pterocarpanquinones: synthesis, antineoplasic activity on cultured human malignant cell lines and TNF-alpha modulation in human PBMC cells.
A new pterocarpanquinone (5a) was synthesized through a palladium catalyzed oxyarylation reaction and was transformed, through electrophilic substitution reaction, into derivatives 5b-d. These compounds showed to be active against human leukemic cell lines and human lung cancer cell lines. Even multidrug resistant cells were sensitive to 5a, which presented low toxicity toward peripheral blood mononuclear cells (PBMC) cells and decreased the production of TNF-alpha by these cells. In the laboratory these pterocarpanquinones were reduced by sodium dithionite in the presence of thiophenol at physiological pH, as NAD(P)H quinone oxidoredutase-1 (NQO1) catalyzed two-electron reduction, and the resulting hydroquinone undergo structural rearrangements, leading to the formation of Michael acceptors, which were intercepted as adducts of thiophenol. These results suggest that these compounds could be activated by bioreduction.
Netto
Chaquip D
CD
Laboratório Integrado Multiusuário II, Instituto Macaé de Metrologia e Tecnologia, Universidade Federal do Rio de Janeiro, Campus Macaé, Brazil.
da Silva
Alcides J M
AJ
Salustiano
Eduardo J S
EJ
Bacelar
Thiago S
TS
Riça
Ingred G
IG
Cavalcante
Moises C M
MC
Rumjanek
Vivian M
VM
Costa
Paulo R R
PR
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D036343:Pterocarpans / Q000138:chemical synthesis* / Q000494:pharmacology*; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
D000970:Antineoplastic Agents; D036343:Pterocarpans; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha