Novel Pt(II) and Pd(II) complexes with polyamine analogues: Synthesis and vibrational analysis

A vibrational spectroscopy study (infrared and Raman) is reported for the biogenic polyamine analogues norspermidine (NSpd), N(1),N(11)-bis(ethyl)norspermine (BENSpm) and N(1)-cyclo-propylmethyl-N(11)-ethylnorspermine (CPENSpm), as well as for their newly synthesised Pt(II) and Pd(II) complexes. Attending to the potential antineoplastic properties of this kind of systems, their full conformational characterization is essential for understanding the molecular basis of their cytotoxic activity and the mechanisms through which they are transported into the cell. The all-trans geometry was found to be favoured for all the alkylated polyamines, in their totally protonated state, while their polynuclear complexes presented a stable geometry very similar to that previously obtained for the analogous chelates with spermidine (M(3)Spd(2)) and spermine (M(2)Spm), comprising two or three cisplatin-like (MCl(2)NH(2)) moieties

QSAR study on the contribution of log P and E(s) to the in vitro antiprotozoal activity of glutathione derivatives.

A series of N-S-blocked glutathione monoester and diester derivatives based on N-benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione were evaluated for activity against the pathogenic parasites Trypanosoma brucei brucei, Trypanosoma cruzi, and Leishmania donovani in vitro.Only monoesters 7-9 with a log P value of >2.7 were active inhibitors of T.b. brucei bloodstream form trypomastigotes. Diester compounds 10-15 and 17-27 in most cases were better inhibitors of T.b. brucei than monoester compounds, and some displayed high activity against T. cruzi 14 and L. donovani 17, 19, 29. Compounds 14, 24, and 25 were the most active compounds identified against T.b. brucei having ED(50) values of <0.4 microM. Analysis of the inhibition data (ED(50)) vs calculated log P and E(s) values provided evidence to support membrane penetration and steric factors as the key component in the activity of these compounds. The optimum values for log P and E(s) determined were 5.8 and -0.70, respectively. A QSAR equation relating log(1/ED(50)) vs log P and E(s) was determined and interpreted within the proposed mechanism of activity for these compounds

Discovery of Novel Alkylated (bis)Urea and (bis)Thiourea Polyamine Analogues with Potent Antimalarial Activities

A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC(50) values in the 100–650 nM range. Analogues arrested parasitic growth within 24 hours of exposure due to a block in nuclear division and therefore asexual development. Moreover, this effect appears to be cytotoxic and highly selective to malaria parasites (>7000-fold lower IC(50) against P. falciparum) and is not reversible by the exogenous addition of polyamines. With this first report of potent antimalarial activity of polyamine analogues containing 3-7-3 or 3-6-3 carbon backbones and substituted terminal urea- or thiourea moieties, we propose that these compounds represent a structurally novel class of antimalarial agents