Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety.

Background: Iztli peptides (IP) are a new class of antibacterial peptides that could be internalized by receptor-mediated endocytosis in yeast. Results: IP-1 penetrates cells independently of endocytosis and makes pores in membranes with large electric potential. Conclusion: Antibacterial peptides like IP-1 make pores or penetrate membranes depending on the membrane potential. Significance: Antibacterial peptides with penetrating activity are robust to control bacterial infections.

A microwave assisted method for the synthesis of some typical 4-substituted oxazolidinone chiral auxiliaries used in asymmetric synthesis is reported in this work. Under these conditions, treatment of (S)-phenylalaninol, (S)-phenylglycinol, (S)-valinol and (1S, 2R)-norephedrine with ethyl carbonate or carbon disulfide under the appropriate and specific microwave reaction conditions, led to an efficient synthesis of some oxazolidin-2-ones, oxazolidine-2-thiones and thiazolidine-2-thiones. The methodology reported in this paper provides these chiral auxiliaries with improved yields and a remarkable reduction on the reaction times, particularly in the case of thiazolidine-2-thiones, as compared with the conventional methods. All the auxiliaries prepared here show spectroscopic data in full agreement with those previously reported in the literature.

<p>We report a systematic study of a series of N-enoyl systems attached to common oxazolidin-2-ones, oxazolidine-2-thiones and thiazolidine-2-thiones chiral auxiliaries in order to determine the most stable conformation of these compounds. ¹H NMR studies show an <em>anti</em>-<em>s</em>-<em>cis</em> structure as the most stable conformation for these series of compounds. Density Functional Theory geometry optimizations and vibrational analysis using the b3lyp exchange-correlation functional with the standard 6-31g** basis sets were done, including solvent effects (chloroform and toluene). Gibbs free energy differences show that the <em>anti</em>-<em>s</em>-<em>cis</em> structures are the most stable conformers lying, on average, ca. 6 kcal/mol lower in energy than the <em>syn</em>-<em>s</em>-<em>cis</em> conformers, widely used to explain the structure and reactivity of <em>N</em>-enoyl systems.</p>