Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity

GLISONI ROMINA, CHIAPETTA DIEGO, FINKIELSZTEIN L., MOGLIONI A. AND SOSNIK ALEJANDRO

NEW JOURNAL OF CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2010 vol. 34 p. 2047 - 2058

1144-0546

The present work thoroughly investigated the aggregationperformance of potentially antiviral 1-indanone TSCs; thisstudy constitutes the first report of its kind. Regardless of therelatively low lipophilicity predicted by theoretical calculations,these compounds are very insoluble in water. Thisperformance is especially notorious for methoxylated (andnon-N-allylated) derivatives. The formation of nano-aggregatesin water was revealed by the appearance of a new strongabsorption peak at 233–239 nm in the UV. DLS analysisshowed that the initially nanoscopic particles (120–300 nm)gradually grew to generate larger structures that remainedinvisible. Results of biological assays in vitro under theseconditions could be seriously misleading, as compounds arenot really dissolved in the culture medium. This phenomenonis even more dramatic when TSC stock aqueous solutions areprepared and used over several weeks assuming that thesolutions remain unaltered.Overall findings point out the strength of the solute–soluteinteraction as the main parameter that rules the solubilizationprocess and stress the relevance of characterizing thoroughlythe solubility and the aggregation of these novel drug candidatesin aqueous media before one proceeds to any biologicalevaluation. For these compounds, solubility predictions basedon theoretical or experimental lipophilicity calculations arenot reliable. Current investigations are being dedicated to gainfurther insight into the crystallization process, the aggregationpattern of these TSCs in culture medium and their potentialstabilization by means of different nanotechnologyapproaches.