Studies of Quinoline Derivatives Interactions with Biomimetic Systems
Pelinson, M. S.*, Rodrigues, M. A., Brandt, C. A., Guedes, C. P., Costa P. L. and Poliiti, M. J.
Instituto de Química, Departamento de Bioquímica da Universidade de São Paulo
Av. Prof. Lineu Prestes, 748, 05508-900, São Paulo
*E-mail: ma_pelinson@yahoo.com.br
Quinoline derivatives have been studied due to their leishmanicidic and antimalarial activities. New synthetic hydroxiquinolines showed better activity and lower toxicity whereas presented the disadvantage of inactivating macrophages (Tempone et al., 2005). A possible way to circumvent this effect is to employ a drug carrier to encapsulate the drug and to deliver it directly onto the parasite. In this study interaction of Quinoline derivatives with biomimetic system, such as micelles, vesicles, and cyclodextrins were realized to determine the physico-chemical parameters for the design of appropriate pharmaceutical formulations.
Ground state prototropic equilibria of two new derivatives, 4-Chloro-2-methyl-3- [(2E)-3-phenylprop-2-enyl]quinoline (CCL) and 3-Allyl-4-chloro-2-methylquinoline (ACl), resulted similar as that of simple quinoline (pKa`s ~5,2).
The association equilibria of CCL and ACl with Hexadecyltrimethylammonium Chloride (CTACl) micelles and b cyclodextryn were studied in two different pH´s (pH=3.0 and pH=8.0), by simple UV-Visible measurements. From the molar extinction coefficients and absorbance wavelength maxima of both CCL and ACL (for the protonated and deprotonated species), the association constants were determined. The results show a favorable interaction of the neutral forms with both biomimetic systems. Present findings allow the adequate selection of encapsulating agents as b cyclodextryn.
Tempone, G. A., Silva, A. C. M. P., Brandt, C. A., Martinez, F. S., Borborema, S. E. T., Silveira, M. A. and Andrade Jr,H. F., Antimicrob. Agents Chemother, 2005,49,1076-1080.
Acknowledgments: CNPq, FAPESP and CAPES.
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