Molecular dynamic study of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin in water: evidences of cooperative effects

MARTINI, M.F; R. GLISONI; A. MOGLIONI; A. SOSNIK; M PICKHOLZ

Villa Carlos Paz, Córdoba

Congreso; Reunión anual de la sociedad de Biofísica Argentina; 2013

SAB

Molecular dynamics study of 1-indanone thiosemicarbazones/hydroxypropyl-β-cyclodextrin complexes formation: evidences of a cooperative effect Martini, M.F.; Glisoni, R.; Moglioni, A.; Sosnik, A. and Pickholz, M. Department of Pharmaceutical Technology, Faculty of Biochemistry and Pharmacy, University of Buenos Aires, C.P. 1113, Buenos Aires, Argentina and CONICET, Buenos Aires, Argentina Among the thiosemicarbazones (TSCs) have been reported varied activities: antineoplastic, antibacterial, antifungal, antiprotozoal and antiviral. In particular, 5,6-dimethoxy-1-indanone TSC was more effective than ribavirin against the virus of the bovine viral diarrhea, the surrogate model of the hepatitis C virus (HCV) [1]. However, TSCs display extremely low aqueous solubility and a relatively high tendency to self-aggregate in water [2]. This behavior hampered the reproducible and reliable evaluation of the biological activity in vitro [1,2]. Cyclodextrins (CDs) are macrocyclic oligosaccharides that combine a hydrophobic nano-sized cavity with a hydrophilic surface. The cavity enables the partial or total incorporation of lipophilic molecules. In this molecular study, we have analyzed the stabilization of inclusion complexes formed between hidroxy-propyl- -cyclodextrin (-HPCD) and two TSC molecules: 1-indanone TSC (1TSC) and 5,6-dimethoxy-1-indanone TSC (2TSC). Our results show a differential stability of the complexes formed according the presence or absence of the substitutents in the indanone ring. Moreover, one type of complex of 2TSC depends of cooperative effects to stabilize and to be formed, which is not the case of the similar complex of 1TSC. References 1- Finkielstein et al Eur J Med Chem. 2008, 43:1767 2- Glisoni et al, New J Chem, 2010, 34:2047