SHORT COMMUNICATION Host–guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study Renato Grillo Æ Nathalie F. S. de Melo Æ Daniele R. de Arau ´jo Æ Gustavo H. G. Trossini Æ Elaine F. F. da Cunha Æ Teodorico de Castro Ramalho Æ Leonardo Fernandes Fraceto Received: 29 April 2009 / Accepted: 1 July 2009 / Published online: 24 July 2009 Ó Springer Science+Business Media B.V. 2009 Abstract Nitroheterocyclic compounds (NC) were can- didate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydro- xymethylnitrofurazone (NFOH), a potential antichagasic compound, with a-cyclodextrin (a-CD), b-cyclodextrin (b-CD), Hydroxypropyl-b-cyclodextrin (HP-b-CD), Dimethyl-b-cyclodextrin (DM-b-CD) and c-cyclodextrin (c-CD) by fluorescence spectroscopy and molecular mod- eling studies. Hildebrand–Benesi equation was used to calculate the formation constants of NFOH with cyclo- dextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-b-CD [ b-CD [ a-CD [ HP-b-CD [ c-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as thera- peutic options for the oral treatment of Chagas disease. Keywords Nitroheterocyclic compound  Cyclodextrins  Fluorescence spectroscopy  Molecular modeling  Inclusion complex Introduction Chagas disease is a serious health problem for people living in Latin America. The nitroheterocyclic hydroxymethy- lnitrofurazone (5-nitro-2-furaldehyde N-(hydroxymethyl)- semicarbazone) (NFOH) has been shown to be active against T. cruzi, the causative agent of Chagas disease and in this way, this compound has been proposed for a new alternative of chemotherapy [1]. Cyclodextrins (CDs) are cyclic oligosaccharides that can be used as a carrier systems for drugs [2, 3] because of their ability to form inclusion complex with different kinds of compounds [4]. Previous works reported some character- ization of the inclusion complex formed between nitro- heterocyclic compounds (NC) and CDs [5–9]. In this study we have been investigated the formation of inclusion complex between NFOH with different cyclodextrins (a-cyclodextrin (a-CD), c-cyclodextrin (c-CD), b-cyclo- dextrin (b-CD), Hydroxypropyl-b-cyclodextrin (HP-b- CD), Dimethyl-b-cyclodextrin (DM-b-CD)) in order to obtain better information about the inclusion phenomena and the rationale for CD selection as an excipient for generate a delivery system for future therapeutic options for the oral treatment of Chagas disease. In order to R. Grillo  L. F. Fraceto (&) Universidade Estadual Paulista Ju ´lio de Mesquita Filho, Campus Sorocaba, Av. Tre ˆs de Marc ¸o, 511, 18087-180 Sorocaba, Sa ˜o Paulo, Brazil e-mail: leonardo@sorocaba.unesp.br N. F. S. de Melo  D. R. de Arau ´jo  L. F. Fraceto Departamento de Bioquı ´mica, Instituto de Biologia, Unicamp, Cidade Universita ´ria Zeferino Vaz, s/n, Campinas, SP, Brazil D. R. de Arau ´jo Universidade Federal do ABC, Santo Andre ´, SP, Brazil G. H. G. Trossini Faculdade de Cie ˆncias Farmace ˆuticas, Universidade de Sa ˜o Paulo, Sa ˜o Paulo, SP, Brazil E. F. F. da Cunha  T. de Castro Ramalho Universidade Federal de Lavras, Campus Universita ´rio da UFLA, Lavras, MG, Brazil 123 J Incl Phenom Macrocycl Chem (2010) 66:417–421 DOI 10.1007/s10847-009-9632-8