Characterisation And Properties Of The Inclusion Complex Of 24-epibrassinolide With β-cyclodextrin

This paper reports the first study of an inclusion complex of a brassinosteroid with β-cyclodextrin. The formation of inclusion complexes between 24-epibrassinolide and β-cyclodextrin was confirmed by their physicochemical properties and the compounds were analysed by differential scanning calorimetry, powder X-ray diffraction, nuclear magnetic resonance spectrometry and scanning electron microscopy. Theoretical calculations using the MM+ HyperChem force field showed a preference for inclusion of the side chain of the epibrassinolide molecule into the β-cyclodextrin cavity to form a 1:1 inclusion complex, although complexes involving inclusion of the steroidal nucleus also possess a favourable interaction energy. Rice lamina inclination assay, employing IAC-103 and IAC-104 cultivars, showed an improved activity for the epibrassinolide-cyclodextrin complex compared to the epibrassinolide itself. The results suggest that brassinosteroid complexation with cyclodextrins may enhance the biological activity of these plant growth regulators.373233240Ahmed, S.M., Improvement of solubility and dissolution of 19-norprogesterone via inclusion complexation (1998) J. Inclusion Phenom. Mol. Rec. Chem., 30, pp. 111-125Alberts, E., Muller, B.W., Complexation of steroid-hormones with cyclodextrin derivatives. Substituent effects of the guest molecule on solubility and stability in aqueous-solution (1992) J. Pharm. Sci., 81, pp. 756-761Braun, P., Wild, A., The influence of brassinosteroids on growth and parameters of photosynthesis of wheat and mustard plants (1984) J. Plant Physiol., 116, pp. 189-196Brutti, C., Apostolo, N.M., Ferrerotti, S.A., Llorente, B.E., Krymkiewicz, N., Micropropagation of Cynara scolymus L. employing cyclodextrins to promote rhizogenesis (2000) Sci. Hortic., 83, pp. 1-10Clouse, S.D., Sasse, J.M., Brassinosteroids: Essential regulators of plant growth and development (1998) Annual Rev. Plant Physiol. Plant Molec. Biol., 49, pp. 427-451Connors, A., The stability of cyclodextrin complexes in solution (1997) Chem. Rev., 97, pp. 1325-1357Cutler, H.G., Yokota, T., Adam, G., (1991) Brassinosteroids: Chemistry, Bioactivity and Applications, ACS Symposium Series, 474. , American Chemical Society, Washington, DCDe Azevedo, M.B.A., Alderete, J.B., Lino, A.C.S., Loh, W., Faljoni-Alario, A., Durán, N., Violacein/β-cyclodextrin inclusion complex formation studied by measurements of diffusion coefficient and circular dichroism (2000) J. Incl. Phenom. Macrocyclic Chem., 37, pp. 67-74De Azevedo, M.B.M., Alderete, J., Zullo, M.A.T., Salva, T.J.G., Duran, N., Brassinosteroids: A new class of plant hormones. The biological activity of 24-epibrassinolide and an inclusion complex of 24-epibrassinolide and β-cyclodextrin (2000) Proceed. Int'l Control. Rel. Bioact. Mater., pp. 5006-5007. , Controlled Release Society, IncDurán, N., De Azevedo, M.B.M., Zullo, M.A.T., Salva, T.J.G., Alderete, J.B., (2000), Process of cyclodextrin/brassinosteroids formulation, for agricultural application, used as plant hormones, Brazilian Patent BR9906202-ADurzan, D.J., Ventimiglia, F.F., (2000), Cyclodextrin nutrients in plant tissue cultures, US Patent US 6087176 [Chem. Abstr. 133: 88976 (2000)]Fujioka, S., Noguchi, T., Takatsuto, S., Yoshida, S., Activity of brassinosteroids in the dwarf rice lamina inclination bioassay (1998) Phytochemistry, 49, pp. 1841-1848Fujioka, S., Sakurai, A., Biosynthesis and metabolism of brassinosteroids (1997) Physiol. Plant., 100, pp. 710-715Gosset, S., Gauvrit, C., (1992), Activity enhancement of benzamide herbicides by cyclodextrins. French 9222204 A1 [Chem. Abstr. 118: 75387 (1997)]Hayashi, T., Iijima, Y., Hoshino, A., Nakamura, M., (1998), Agents and method for flowering acceleration using cinnamic acid-cyclodextrin inclusion compounds Japanese Patent. Kokai Tokkyo Koho JP 10273404 A2 [Chem. Abstr. 129: 327304 (1999)]Huet, H., Jullien, M., The β-cyclodextrins delay the germination of the somatic embryos of carrot (Daucus carota L.) (1992) Acad. Sci., Ser. III, 314, pp. 171-177Ikekawa, N., Zhao, Y., Application of 24-epibrassinolide in agriculture (1991) Brassinosteroids: Chemistry, Bioactivity and Applications. ACS Symposium Series, 474, pp. 280-305. , Cutler H.G., Yokota T. and Adam G. (eds). American Chemical Society, Washington, DCKalinch, F.N., Mandava, N.B., Todhunter, J.A., Relationship of nucleic acid metabolism to brassinolide-induced responses in bean (1985) J. Plant Physiol., 120, pp. 207-214Khripach, V.A., Zhabinskii, V.N., De Groot, A.E., (1999) Brassinosteroids, A New Class of Plant Hormones, , Academic Press, Harcourt Brace & Company, USAKoehler, G., Grabner, G., Klein, C.T.H., Marconi, G., Mayer, B., Monti, S., Structure spectroscopic properties of cyclodextrin inclusion complexes (1996) J. Inc. Phenom. Mol. Rec. Chem., 25, pp. 103-108Lipkowitz, K.B., Applications of computational chemistry to the study of cyclodextrins (1998) Chem. Rev., 98, pp. 1829-1873Mandava, N.B., Plant growth promoting brassinosteroids (1988) Ann. Rev. Plant Physiol. Plant Mol. Biol., 39, pp. 23-52Marquart, V., Adam, G., Recent advances in brassinosteroids research (1991) Chemistry of Plant Protection, Herbicide Resistance - Brassinosteroids, Gibberellins, Plant Growth Regulators, 7, pp. 104-139. , Ebing W. (ed.). Springer-Verlag, BerlinMarzona, M., Carpignano, R., Quagliotto, P., Quantitative structure-stability relationships in the inclusion complexes of steroids with cyclodextrins (1992) Annal. Di Chim., 82, pp. 517-537Okii, M., (1993), Cyclodextrins for enhanced callus tissue culture of rice Japanese Patent. Kokai Tokkyo Koho JP 05292955 A2 [Chem. Abstr. 120: 1324504 (1997)]Rajagopalan, N., Chen, S.C., Chow, W.S., A study of the inclusion complex of amphotericin-B with cyclodextrin (1986) Int. J. Pharm., 29, pp. 161-168Sairam, P.K., Effect of homobrassinolide application on plant metabolism and grain yield under irrigated and moisture stress conditions of two wheat varieties (1994) Plant Growth Regul., 14, pp. 173-181Sakurai, A., Fujioka, S., The current status of physiology and biochemistry of brassinosteroids (1993) Plant Growth Regul., 13, pp. 147-159Sasse, J.M., Recent progress in brassinosteroid research (1997) Physiol. Plant., 100, pp. 696-701Sawamoto, T., (2000), Plant growth-stimulating and disease-preventing agents containing 1-triacontanol and their manufacture Japanese Patent 2000128707 A2 [Chem. Abstr. 132:304657]Stella, V.J., Rajewski, R.A., Cyclodextrins: Their future in drug formulation and delivery (1997) Pharm. Res., 14, pp. 556-567Stella, V.J., Rao, V.M., Zannou, E.A., Zia, V., Mechanisms of drug release from cyclodextrin complexes (1999) Adv. Drugs Del. Rev., 36, pp. 3-16Szejtli, J., Szente, L., Harshegyi, J., Daroczi, I., Vorashazy, L., Torok, S., (1989), Inclusion complexes and mixtures of plant growth regulators with cyclodextrins., Hung. 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Reaction Of Methyl (e)-2-phenyl-1-azirine-3-acrylates With Hydrazines And Amidines. Synthetic And Mechanistic Implications

1-Azirines 2a-b react with hydrazine in methanol to produce hexahydropyrrolo[3,2-c]pyrazol-5-ones 3a-b. The process is suggested to involve intramolecular interception of an unstable 4-aminopyrazoline intermediate resulting from C=N bond cleavage. Reaction of 2a with phenylhydrazine similarly affords 3c. In dimethyl sulfoxide, on the other hand, formamidine, guanidine, and hydrazine afford imidazole 4, pyrimidines 5a-b, amino-s-triazine 6, or triazole 9 as a consequence of C-C bond cleavage in aziridine intermediate 8. The intermediacy of tautomers is proposed to account for the diversity of products in this case. © 1991 American Chemical Society.5617

Dehydrocrotonin And Its β-cyclodextrin Complex: Cytotoxicity In V79 Fibroblasts And Rat Cultured Hepatocytes

Trans-dehydrocrotonin has antiulcerogenic and antitumor activities. A complex of β-cyclodextrin with dehydrocrotonin was developed to improve the delivery of dehydrocrotonin. Complex in solid state was evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). X-ray diffraction and scanning electron microscopy studies showed that dehydrocrotonin exists in a semicrystalline state in the complexed form with β-cyclodextrin. Differential scanning calorimetry studies showed the existence of a complex of dehydrocrotonin with β-cyclodextrin. The thermal gravimetric analysis studies confirmed the differential scanning calorimetry results of the complex. Free dehydrocrotonin and the dehydrocrotonin/β-cyclodextrin inclusion complex were assayed in freshly isolated rat hepatocytes and in V79 cells. Cytotoxicity was determined using nucleic acid content, methylthiazoletetrazolium (MTT) reduction and neutral red uptake assays. In all assays, there was a large reduction (3.5-16.1-fold) in the cytotoxicity of dehydrocrotonin in hepatocytes when complexed with β-cyclodextrin, whereas for V79 cells the decrease in cytotoxicity was 1.7- and 1.87-fold for MTT reduction and nucleic acid content assays, respectively. The lower cytotoxicity of the dehydrocrotonin/β-cyclodextrin complex compared to free dehydrocrotonin in rat hepatocytes and V79 cells suggests that such a complex may be useful for the administration of dehydrocrotonin in vivo. © 2005 Elsevier B.V. All rights reserved.5101-21724Agner, A.R., MacIel, M.A., Pinto, A.C., Colus, I.M., Antigenotoxicity of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara (2001) Planta Med., 67, pp. 815-819Anazetti, M.C., Melo, P.S., De Azevedo, M.B.M., De Carvalho, C.A., Durán, N., Haun, M., β-Cyclodextrin complexed with dehydrocrotonin induces apoptosis in HL60 cells as seen by flow cytometry (2004) XII Congress of the Brazilian Society for Cell Biology and IX Ibero-American Congress of Cell Biology. Brazil: Campinas, I-012Bianchi, V., Fortunati, E., Cellular effects of an anionic surfactant detected in V79 fibroblasts by different cytotoxicity tests (1990) Toxicol. in Vitro, 4, pp. 9-16Bibby, D., Davies, N.M., Tucker, I.G., Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems (2000) Int. J. Pharm., 197, pp. 1-11Borefreund, E., Puerner, J.A., A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR 90) (1984) J. Tissue Cult. Methods, 9, pp. 7-9Cingi, M.R., De Angelis, I., Fortunati, E., Reggiani, D., Bianchi, V., Tiozzo, R., Zucco, F., Choice and standardization of test protocols in cytotoxicology: A multicentre approach (1991) Toxicol. in Vitro, 5, pp. 119-125De Azevedo, M.B.M., Alderete, J.B., Lino, A.C.S., Loh, W., Faljoni-Alario, A., Durán, N., Violacein/β-cyclodextrin inclusion complex formation studied by measurements of diffusion coefficient and circular dichroism (2000) J. Ind. Phenom. Mol. Recognit. Chem., 37, pp. 67-74De Azevedo, M.B.M., Zullo, M.A.T., Alderete, J.B., De Azevedo, M.M.M., Durán, N., Characterization and properties of the inclusion complex of 24-epibrassinolide with β-cyclodextrin (2002) Plant Growth Regul., 37, pp. 233-240Denizot, F., Lang, R., Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability (1986) J. Immunol. Methods, 89, pp. 271-277Griffiths, D.W., Bender, M.L., Orientational catalysis by cyclohexaamylose (1973) J. Am. Chem. Soc., 95, pp. 1679-1680Grynberg, N.F., Echevarria, A., Lima, J.E., Pamplona, S.S.R., Pinto, A.C., MacIel, M.A., Anti-tumour activity of two 19-nor-clerodane diterpenes, trans-dehydrocrotonin and trans-crotonin, from Croton cajucara (1999) Planta Med., 65, pp. 687-689Guguen-Guillouzo, C., Guillouzo, A., Methods for preparation of adult and fetal hepatocytes (1986) Research in Isolated and Cultured Hepatocytes, pp. 1-12. , A. Guillouzo C. Guguen-Guillouzo Les Editions John Libbey Eurotext London, UKHirayama, F., Uekama, K., Cyclodextrin-based controlled drug release system (1999) Adv. Drug Deliv. Rev., 36, pp. 125-141Hiruma-Lima, C.A., Spadari-Bratfisch, R.C., Kassisse, D.M., Souza-Brito, A.R.M., Antiulcerogenic mechanisms of dehydrocrotonin, a diterpene lactone obtained from Croton cajucara (1999) Planta Med., 65, pp. 325-330Katzer, A., Marquardt, H., Westendorf, J., Wening, J.V., Von F., G., Polyetheretherketone-cytotoxicity and mutagenicity in vitro (2002) Biomaterials, 23, pp. 1749-1759Loftsson, T., Pharmaceutical applications of β-cyclodextrins (1999) Pharm. Technol. Europe, 11, pp. 20-32Melo, P.S., Durán, N., Haun, M., Derivatives of dehydrocrotonin, a diterpene lactone isolated from Croton cajucara: Cytotoxicity in rat cultured hepatocytes and in V79 cells (2002) Human Exp. Toxicol., 21, pp. 281-288Mura, P., Faucci, M.T., Parrini, P.L., Furlanetto, S., Pinzauti, S., Influence of the preparation method on the physicochemical properties of ketoprofen-cyclodextrin binary systems (1999) Int. J. 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Violacein/β-cyclodextrin Inclusion Complex Formation Studied By Measurements Of Diffusion Coefficient And Circular Dichroism

The formation of inclusion compounds between violacein and β-cyclodextrin was studied by diffusion and circular dichroism measurements. The present work was undertaken to explore the feasibility of the β-cyclodextrin in reducing the toxicity and enhancing the antitumoral efficacy of violacein by forming an inclusion complex. The results of the two experiments are in good agreement, suggesting the formation of 1 : 1 and 1 : 2 complexes. The diffusion coefficient measurements enabled estimates of the sizes of the complexes involved. From the circular dichroism and computational calculations it was possible to view a preference for inclusion of the most polar part of the molecule to form a 1 : 2 inclusion complex. We expect that this work proves the potential of these techniques to determining complex stoichiometry.3701/04/156774Bortolus, P., Monti, S., (1996) Advances in Photochemistry, 21, p. 1. , D. C. Neckers, D. H. Volman and G. von Bün Wiley-Interscience, New YorkLipkowitz, K.B., (1998) Chem. Rev., 98, p. 1829Dekharsky, M.V., Inoue, Y., (1998) Chem. Rev., 98, p. 1875Saenger, W., (1980) Angew. Chem. Int. Ed. Engl., 19, p. 344Parker, D., Kataky, R., (1997) J. Chem. Soc., Chem. Commun., 2, p. 141Connors, K.A., (1997) Chem. Rev., 97, p. 1325Stella, V.J., Rajewski, R.A., (1997) Pharm. Res., 14, p. 556Koehler, G., Grabner, G., Klein, C.T.H., Marconi, G., Mayer, B., Monti, S., Rechthaler, K., Wolschann, P., (1996) J. Incl. Phenom. Mol. Recognit. Chem., 25, p. 103Beezer, A.E., Mitchell, J.C., (1992) Andrews: Pestic. Sci., 35, p. 375Loh, W., Beezer, A.E., Mitchell, J.C., (1994) Lagmuir, 10, p. 3431Lino, A.C.S., Loh, W., J. Incl. Phenom. Mol. Recognit. Chem., p. 1998. , submittedCohen, A.G.Y., (1997) J. Org. Chem., 62, p. 120Li, M.-X., Li, N.-Q., Gu, Z.-N., Zhou, N.-H., Sun, Y.-L., Wu, Y.-Q., (1996) Electrochim. Acta., 41, p. 2877Manzanares, M.I., Solis, V., De Rossi, R.H., (1996) J. Electroanal. Chem., 407, p. 141Uekama, K., Otagiri, M., Kanie, Y., Tanaka, S., Ikeda, K., (1975) Chem. Pharm. Bull., 23, p. 1421Nakahara, H., Tanaka, H., Kukuda, K., Matsumoto, M., Tagaki, W., (1990) Thin Solid Films, p. 284Guo, R., Chang, J., Lin, S., Chen, R., Hu, J., Zhang, H., (1996) Guangpuxue Yu Guangpu Fenxi., 16, p. 38(1994) Chem. Abstr., 125, p. 86074Hamai, S., (1997) J. Incl. Phenom. Mol. Recognit. Chem., 27, p. 57Mayer, B., Marconi, G., Klein, C., Köhler, G., Wolschann, P., (1997) J. Incl. Phenom. Mol. Recognit. Chem., 29, p. 79Marconi, G., Mayer, B., (1997) Pure Appl. Chem., 69, p. 779Wu, Y., Jin, J., (1966) Sichuan Daxue Xuebao, Ziran Kexueban., 33, p. 560(1997) Chem. Abstr., 126, p. 317579Shen, X., Belletête, M., Durocher, G., (1998) J. Phys. Chem. B, 102, p. 1877Harada, A., Lin, J., Kamachi, M., (1992) Nature, 356, p. 325Harada, A., Lin, J., Kamachi, M., (1994) Nature, 370, p. 126Durán, N., Faljoni-Alario, A., (1980) An. Acad. Brasil. Ciên., 52, p. 287Rettori, D., Durán, N., (1998) World J. Microbiol. Biotechnol., 14, p. 685Haun, M., Pereira, M.F., Hoffmann, M.E., Riveros, R., Joyas, A., Campos, V., Durán, N., (1992) Biol. Res., 25, p. 21Durán, N., Antônio, R.V., Haun, M., Pilli, R.A., (1994) World J. Microbiol. Biotechnol., 10, p. 686Durán, N., Erazo, S., Campos, V., (1983) An. Acad. Brasil. Ciênc., 55, p. 231(1984) Chem. Abstr., 100, pp. 48417bDurán, N., Melo, P.S., Haun, M., (1996) Proc. XXV Annual Meeting Brazilian Biochemical Society, p. 150. , (Escritorio & Editorial, São Paulo, S.P., Brazil), Caxambu, M.G., Brazil O-24Durán, N., Melo, P.S., Haun, M., Proc. VIII Brazilian National Meeting in Virology, p. 1996. , (Brazilian Soc. Virology Publ., UNESP, Jaboticabal, S. P., Brazil), São Lourenço, M.G., BrazilMelo, P.S., Haun, M., Durán, N., (1997) FASEB J., 11 (SUPPL.), pp. A1418Durán, N., Haun, M., Brazilian Patent PI 9702918 (1997)Singh, U.V., Udupa, N., (1997) Indian J. Physiol. Pharmacol., 41, p. 171Singh, U.V., Udupa, N., (1997) Pharm. Sci., 3, p. 573Loh, W., Tonegutti, C.A., Volpe, P.L.O., (1993) J. Chem. Soc. Faraday Trans., 89, p. 113Akizadeth, A., Nieto De Castro, C.A., Wakeham, W.A., (1980) Int. J. Thermophys., 1, p. 243Price, W.E., Trickett, R.A., Harris, K.R., (1989) J. Chem. Soc. Faraday Trans. 1, 85, p. 3281Eastel, A.E., Woolf, L.A., (1989) J. Chem. Soc. Faraday Trans. 1, 80, p. 1287Noulty, R.A., Leaist, D.G., (1987) J. Chem. Eng. Data, 32, p. 418Grabner, G., Monti, S., Marconi, G., Mayer, B., Klein, C., Köhler, G., (1996) J. Phys. Chem., 100, p. 2006

Evaluation Of The Antiulcerogenic Activity Of Violacein And Its Modulation By The Inclusion Complexation With β-cyclodextrin

The effects of β-cyclodextrin (βCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied. Violacein-βCD inclusion complexes were prepared in 1:1 and 1:2 molar ratios and analysed by differential scanning calorimetry and powder X-ray diffractometry. Violacein previously administered orally at 10 mg/kg significantly reduced indomethacin-induced gastric lesions, as well as 100 mg/kg of cimetidine (positive control). However, βCD complexation in both molar ratios significantly potentiated the protective action of violacein. In the HCl-ethanol-induced gastric ulcer model, violacein and the 1:2 inclusion complex (10 mg/kg, p.o.) inhibited gastric damage by almost 85%, whereas a 63% reduction was observed for the positive control, lansoprazole, at 30 mg/kg. In contrast, treatment with the 1:1 inclusion complex resulted in almost total disappearance of the antiulcer activity in this model. No significant changes in stress-induced gastric injury were found. In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein. In summary, the 1:2 βCD inclusion complex has gastroprotective properties similar to or higher than that of violacein. An increase in mucosal defensive mechanisms and protection against peroxidative damage might be involved.814387396Ahmed, M.O., El-Gibaly, I., Ahmed, S.M., Effect of cyclodextrins on the physicochemical properties and antimycotic activity of clotrimazole (1998) Int. J. 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Colorectal Cancer Chemoprevention By 2 β-cyclodextrin Inclusion Compounds Of Auraptene And 4′-geranyloxyferulic Acid

The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4′-geranyloxy-3′-methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with b-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/ dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/β-CD or AUR/β-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/β-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 ± 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/b-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/β-CD and AUR/β-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-α, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1β, which were induced in the adenocarcinomas. 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Biological Activities Of Violacein, A New Antitumoral Indole Derivative, In An Inclusion Complex With β-cyclodextrin

Violacein is a poorly water-soluble antitumoral and antibacterial drug. The solubility can be enhanced by complexation with β-cyclodextrin. The inclusion complex was prepared by the co-precipitation method in molar ratios of 1 : 1 and 1 : 2 of violacein/β-cyclodextrin, respectively. The acute toxicity (E. coli strain) of violacein did not change up to 400 μM, either in the presence or absence of cyclodextrin. Cytotoxicity (V-79 cell culture) through DNA and MTT assays was significantly decreased in the presence of the 1 : 2 molar ratio complex. Studies on erythrocyte lipid peroxidation by the thiobarbituric acid (TBA) method showed that violacein and violacein/β-CD (1 : 2) at 100 μM cause 50% and 80% inhibition, respectively. At 500 μM the violacein/β-CD complex inhibited lipid peroxidation completely; however, with free violacein only 65% inhibition was reached at that concentration.3701/04/1593101Irie, T., Uekema, K., (1997) J. Pharm. Sci., 86, p. 147Loftsson, T., Brewster, M.E., (1997) Pharm. Technol. Eur., 9, p. 26Stella, V.J., Rajewski, R.A., (1997) Pharm. Res., 14, p. 556Szejtli, J., (1997) J. Mater. Chem., 7, p. 575Ueda, H., (1998) Zairyo Gijutsu, 16, p. 11(1998) Chem. Abstr., 128, pp. 158-784Kata, M., Aigner, Z., Eros, I., (1998) Acta Pharm. Hung., 68, p. 107Loftsson, T., Stefansson, E., Fridriksdottir, H., Kristinsson, J.K., (1996) Proc. 8th Int. Symp. Cyclodextrin, p. 407. , J. Szejtli and L. Szente (eds.), Kluwer Academic Publishers, DordrechtSavolainen, J., Jarvinen, K., Taipale, H., Jarho, P., Loftsson, T., Jarvinen, T., (1998) Pharm. Res., 15, p. 1696Dhanaraju, M.D., Kumaran, K.S., Baskaran, T., Moorthy, M.S.R., (1998) Drug Dev. Ind. Pharm., 24, p. 583Ahmed, M.O., El-Gibaly, I., Ahmed, S.M., (1998) Intern. J. Pharm., 171, p. 111Nigam, S., Durocher, G., (1997) J. Photochem. Photobiol. A, 103, p. 143De, R., Sinha, S., Ganguly, T., (1997) Nuovo Cimento Soc. Ital. Fis. D, 19 D, p. 955De Azevedo, M.B.M., Alderete, J.B., Lino, A.C.S., Loh, W., Faljoni-Alario, A., Durán, N., (2000) J. Incl. Phenom., 37, p. 67. , this issueRettori, D., Durán, N., (1998) World J. Microbiol. Biotechnol., 14 (5), p. 685Haun, M., Pereira, M.F., Hoffmann, M.E., Riveros, R., Joyas, A., Campos, V., Durán, N., (1992) Biol. Res., 25, p. 21Durán, N., Antônio, R.V., Haun, M., Pilli, R.A., (1994) World J. Microbiol. Biotechnol., 10, p. 686Durán, N., Erazo, S., Campos, V., (1983) An. Acad. Bras. Ci., 55, p. 231(1984) Chem. Abstr., 100, pp. 48417bDurán, N., Melo, P.S., Haun, M., (1996) XXV Annual Meeting Brazilian Biochemical Society, p. 150. , (Escritorio & Editorial, São Paulo, S.P., Brazil), Caxambu, M.G. Brazil, Abstr. O-24Durán, N., Melo, P.S., Haun, M., (1996) VIII Brazilian National Meeting in Virology, p. 179. , (Brazilian Soc. Virology Publ., UNESP, Jaboticabal, S.P., Brazil), São Lourenço, M.G., Brazil, AbstrMelo, P.S., Maria, S.S., Vidal, B.C., Haun, M., Durán, N., (1999) In Vitro Cell. Develop. Biol., , In pressDe Conti, R., Oliveira, D.A., Fernandes, A.M.A.P., Melo, P.S., Rodriguez, J.A., Haun, M., De Castro, S.L., Durán, N., (1998) In Vitro Mol. Toxicol., 11, pp. 153-160Huveneers-Oorsprong, M.B.M., Hoogenboom, L.A.P., Kuiper, H.A., (1997) Toxicol. In Vitro, 11, p. 385Cingi, M.R., Fortunati, E., Reggioni, D., Bianchi, V., Tiozzo, R., Zucco, F., (1991) Toxicol. In Vitro, 5, p. 119Scudiero, D.A., Shoemaker, P.H., Paul, K.D., Monks, A., Tierney, S., Nofziger, T.H., Currens, M.J., Boyd, M.R., (1988) Cancer Res., 48, p. 4827Jardim, W.F., Gimenez, S.M.M., Canela, M.C., Moraes, S.G., (1993) Chem. Spec. Bioavailab., 5, p. 97Stocks, J., Dormandy, T.L., (1971) Br. J. Haematol., 20, p. 95Rettori, D., Rodrigues, R.A., Durán, N., (1998) Rev. Farm. Bioquim. Univer. São Paulo (Brazil), 34 (SUPPL. 1), p. 169Melo, P.S., Haun, M., Durán, N., (1996) XXV Ann. Meeting. Brazilian Biochem. Soc., p. 148. , (Escritorio & Editorial, São Paulo, S.P., Brazil), Caxambu, M.G. Abstr. O-10Maria, S.S., Melo, P.S., Vidal, B.C., Durán, N., Haun, M., (1998) XXVII Ann. Meeting. Brazilian Biochem. SDC, p. 89. , (Tec-Art Editora Ltda., São Paulo, S.P., Brazil), Caxambu, M.G. Brazil. Abstr. I-36De Souza, A.O., Aily, D.C.G., Sato, D.N., Durán, N., (1999) Rev. Inst. Adolfo Lutz (Brazil), 58, p. 1