Improving the solubility of an antifungal thiazolyl hydrazone derivative by cyclodextrin complexation.

RN104, named 2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole, is a thiazolyl hydrazone derivative with promising antifungal activity. A HPLC-DAD method was carried out using C18 end-capped column (250 × 4.6 mm, 5 µm) and a mobile phase composed of water and acetonitrile (15:85 v/v) at a flow rate of 1.2 mL/min, injection volume 25 μL and DAD detection at 240 nm. The method showed to be selective, linear in the range of 20 to 240 µg/mL, precise, accurate and robust.Due to the low solubility of RN104 in water, the development of inclusion complexes using different cyclodextrins (β-CD, γ-CD and 2-HP-β-CD) was investigated, as well as the interaction mode between RN104 and cyclodextrins using molecular docking followed by semi-empirical calculations. Among tested cyclodextrins, the best results were obtained with 2-HP-β-CD, which promoted an 18-fold increase in RN104's aqueous solubility.