Antileishmanial activity is reported for the first time for saponins of ivy, Hedera helix L., in vitro on promastigote and amastigote forms of Leishmania infantum and Leishmania tropica. The compounds tested were an extract containing 60% of saponic complex (CS 60), the bidesmosides hederasaponin B, C, and D (saponin K10), their corresponding monodesmosides alpha-, beta-, and delta-hederin, and hederagenin. CS 60 and bidesmosides have shown no effect. Monodesmosides were found to be as effective on promastigote forms as the reference compound (pentamidine). Against amastigote forms only hederagenin exhibited a significant activity which was equivalent to that of the reference compound (N-methylglucamine antimonate).
Purpose This study evaluated mechanistic diVerences of pralatrexate, methotrexate, and pemetrexed. Methods Inhibition of dihydrofolate reductase (DHFR) was quantiWed using recombinant human DHFR. Cellular uptake and folylpolyglutamate synthetase (FPGS) activity were determined using radiolabeled pralatrexate, methotrexate, and pemetrexed in NCI-H460 non-small cell lung cancer (NSCLC) cells. The tumor growth inhibition (TGI) was assessed using MV522 and NCI-H460 human NSCLC xenografts. Results Apparent K i values for DHFR inhibition were 45, 26, and >200 nM for pralatrexate, methotrexate, and pemetrexed, respectively. A signiWcantly greater percentage of radiolabeled pralatrexate entered the cells and was polyglutamylatated relative to methotrexate or pemetrexed. In vivo, pralatrexate showed superior anti-tumor activity in both NSCLC models, with more eVective dose-dependent TGI in the more rapidly growing NCI-H460 xenografts. Conclusions Pralatrexate demonstrated a distinct mechanistic and anti-tumor activity proWle relative to methotrexate and pemetrexed. Pralatrexate exhibited enhanced cellular uptake and increased polyglutamylation, which correlated with increased TGI in NSCLC xenograft models.
As part of our screening of antiviral agents from medicinal plants, 11 compounds from plant origin (Bupleurum rigidum and Scrophularia scorodonia), three saikosaponins, seven iridoids and one phenylpropanoid glycoside were tested in vitro against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. Five of these compounds showed antiviral activity against VSV. The percentages of cellular viability at the non-toxic limit concentrations of the active compounds were: verbascoside 53.6 % at 500 microg/ml, 8-acetylharpagide 32.1 % at 500 microg/ml, harpagoside 43.3 % at 450 microg/ml, scorodioside 47.8 % at 500 microg/ml and buddlejasaponin IV 56.9 % at 25 microg/ml. Although none of the saikosaponins were active against HSV-1, the iridoid scorodioside showed moderate in vitro anti-HSV-1 activity (30.6 % at 500 microg/ml). However, none of the compounds tested in this survey had any effect against poliovirus.
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