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Abstract: 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-α 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. [Copyright &y& Elsevier]

Abstract: We investigated a synthetic coumestan named LQB93 and similar compounds abilities to antagonize activities of Bothrops jararacussu and Bothrops jararaca crude venoms in different protocols. The antimyotoxic activity was evaluated in vitro by the rate of release of creatine kinase (CK) from isolated mouse extensor digitorum longus muscle (EDL) induced by B. jararacussu (25g/ml). For in vivo studies, B. jararacussu venom (1.0mg/kg) was preincubated with LQB93 (0.1–30mg/kg), during 30min, for later injection in mouse tight and evaluation of the antimyotoxic and anti-edematogenic effects. LQB93 antagonized in vitro, the increase of CK release from the EDL muscle (IC50 =0.0291M). It also showed in vivo, antimyotoxic and anti-edematogenic effects that were dose-dependent with ID50 of 0.17mg/kg and 0.14mg/kg, respectively. The hemorrhage induced by B. jararaca (1.0mg/kg) venom in the mouse skin, was abolished by LQB93 (10.0mg/kg) preincubated with venom. Like wedelolactone, LQB93 protected rat isolated heart on a Langendorff preparation, from the cardiotoxicity of B. jararacussu venom. LQB93 inhibit the effects of Bothrops venoms like wedelolactone, a natural compound isolated from the plant Eclipta prostrata. [Copyright &y& Elsevier]

Abstract: Naturally occurring pterocarpans 1a,b, pterocarpan 1c, isoflavane 2 and ortho-quinone 3 were synthesized in the racemic form and their cytotoxic effect was evaluated on the human leukemia cell lines K562 (resistant to oxidative stress), Lucena-1 (MDR phenotype) and HL-60. Ortho-quinone 3 (IC50 =1.5μM, 1.8μM and 0.2μM, respectively) and catechol pterocarpan 1a (IC50 =3.0μM, 3.7μM and 2.1μM, respectively) were the most active compounds on these cells and were also evaluated on other human leukemia cell lines (Jurkat and Daudi). Ortho-quinone 3 was 2 to 10 times more potent than pterocarpan 1a, depending on the cell line considered, however, showed a greater toxicity for lymphocytes activated by PHA. [Copyright &y& Elsevier]

Abstract: Nitrones 4–7, structurally related to PBN (1), were prepared by reaction of the corresponding aromatic aldehydes with N-tert-butyl hydroxylamine. The protective effects of these nitrones against microvascular damages in ischemia/reperfusion in the ‘hamster cheek pouch’ assay were studied and 1, as well as 4a, 4b, and 7 (derived from piperonal, O-benzyl vanillin, and furfural, respectively), showed to be more active than shark cartilage or α-tocopherol. No correlation was found between the protective effect of these nitrones and their log P (partition coefficient) or their capacity to trap ·OH and ·CH3 radicals. [Copyright &y& Elsevier]

Abstract: Two 5-deoxypterocarpens, one pterocarpen, and one coumestan were prepared from deoxychromenes, chromenes, and ortho-iodophenols. The key step in the described synthetic approach is an intramolecular Heck reaction leading to the formation of the C-ring present in the structure of these compounds. [Copyright &y& Elsevier]