This work focuses on the interaction of rifabutin (RFB), a naphthalenic ansamycin, with membrane models. Since the therapeutic and toxic effects of this class of drugs are strongly influenced by their lipid affinity, we concerned specifically on the ability of this antibiotic to affect the membrane biophysical properties. The extent of the interaction between RFB and membrane phospholipids was quantified by the partition coefficient (K(p)), using membrane model systems that mimic the human (liposomes of 1,2-dimyristoyl-sn-glycero-phosphocholine, DMPC) and the bacterial (liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DMPG) plasma membranes. To predict the drug location in the membranes, fluorescence quenching and lifetime measurements were carried out using the above-mentioned membrane models labeled with fluorescent probes. Steady-state anisotropy measurements were also performed to evaluate the effect of RFB on the microviscosity of the membranes. Overall, the results support that RFB has higher affinity for the bacterial membrane mediated by electrostatic interactions with the phospholipid head groups.

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Octyl and dodecyl glycosides possessing 2-deoxy-arabino-hexopyranoside moieties belonging to the D-and L-series in their alpha-and beta-forms were synthesized by reaction of an acetyl protected glycal with octanol or dodecanol, catalyzed by triphenylphosphine hydrobromide, followed by deprotection. Their surface properties were studied and discussed in terms of the adsorption and aggregation parameters, pC(20), CMC, and gamma(CMC). The antimicrobial activities were assessed using the paper disk diffusion and broth dilution methods. Both the octyl and dodecyl 2-deoxy beta-D-glycosides inhibited significantly Enterococcus faecalis, a microbe also highly susceptible to dodecyl 2,6-dideoxy-alpha-L-arabino-hexopyranoside. This compound was particularly active against Bacillus cereus and Bacillus subtilis, presenting for both Bacillus species a minimal inhibitory concentration of the same order of magnitude and a minimal lethal concentration even smaller than that obtained for chloramphenicol, a bioactivity which remained unaltered after 1 year solution storage at 4 degrees C. In addition, activity over Listeria monocytogenes was also observed. Direct cytotoxicity and genotoxicity of the glycosides were determined by proliferative index (mitotic index) evaluation in peripheral human lymphocytes of healthy donors. All compounds induced acute toxicity effects, and the response was dose dependent for the alpha-anomer of both the alkyl 2-deoxy-arabinohexopyranosides and for the corresponding dodecyl beta-anomer, what suggests that nontoxic but still bioactive concentrations may be found for these compounds.

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