V L Eifler-Lima | Search PubMed

PubMed2001

Ofloxacin/beta-cyclodextrin complexation.

Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with beta-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and 1H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and beta-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling.

Anti-Infective Agents↗

PubMedDate not supplied

Inhibition of tumor growth and polyamine uptake by tetracyclic amidines bearing a putrescine moiety.

Tetracyclic amidines (tetrahydroquino[4.3-b][l]benzazepine: compound 11 and tetrahydrobenzo[k]naphthyridine: compound 12) bearing a putrescine moiety possess significant DNA-binding affinity. We report here that these compounds and their a and b isomers inhibit tumor cell growth and putrescine uptake in 3LL carcinoma cells in vitro. Moreover, compound 11 reduced by 50% the accumulation of putrescine in intestinal brush border membrane vesicles. In CHO-MG, a cell line deficient for the specific polyamine uptake system, the cytotoxicity of these compounds was significantly reduced compared to the CHO wild cell line. The IC50 for CHO-MG was significantly higher than for CHO, demonstrating that the polyamine transport system increased the efficacy of these compounds. The efficacy of compounds 11 and 12 might therefore be related to their ability to interact with DNA as well as their structural analogy with polyamines. Moreover, we clearly show that DFMO enhances the efficacy of these tetracyclic amidines in vivo. Potential mechanisms include: a) lower intracellular polyamine levels reduces polyamine DNA-stabilizing functions, increasing accessibility for DNA-binding drugs; b) DFMO enhances the polyamine uptake system in tumor cells, increasing the entry of tetracyclic amidines bearing a putrescine moiety as well as their accessibility to final DNA-binding sites. The fact that natural polyamine uptake is reduced by the same compounds constitutes an additive mechanism for antitumoral efficiency.

Amidines↗