Ursolic acid (UA) is being investigated due to its anti-inflammatory potential, and structural modifications can enhance its biological activities. The aim of this study was to evaluate the immunomodulatory effect of the ursolic acid derivatives (UAD) in macrophages and in the carrageenan-induced paw edema model. RAW264.7 cells were cultured in the presence or absence of UA or UAD (1-18). Nitric oxide (NO), nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF), and cellular viability were measured. 30 min before the carrageenan-induced paw edema, the UAD1 and UAD2 (200 mg kg-1) were administered intraperitoneally. The results showed that UAD2-4, UAD7, UAD9-11 had half maximal inhibitory concentration (IC50) greater than 90 µM and were able to reduce NO, NF-κB and TNF production. Moreover, UAD1 and UAD2 reduced paw edema and IL-6 production. In conclusion, the results obtained demonstrated a variation in the response between the derivatives due to the chemical modifications, showing potential to reduce the inflammatory mediators, deserving further investigations.

This study searched for a new pre-formulation based on the natural compound from the class of the avermectins, named abamectin (ABA), in order to improve its action against Aedes aegypti larvae by complexation with β-cyclodextrin (βCD). Concerning the low aqueous solubility of ABA, even in the presence of βCD, it was also invoked the strategy of working with hydrophobic nanoprecipitates (HNPs). For these purposes, molecular and supramolecular characterizations of 1:1 ABA/βCD complex and evaluation of its toxicity against A. aegypti larvae were performed. In the physical-chemistry characterizations, changes in the infrared spectra and thermal profiles in relation to precursors confirmed the occurrence of interactions between ABA and βCD in solid state. Nuclear magnetic resonance (NMR) data suggest the inclusion of ABA in βCD via benzofuran ring. Isothermal titration calorimetry (ITC) experiments allowed to verify the formation of complex with a 1:1 stoichiometry, which was entropy driven. The dynamic light scattering and zeta potential data from inclusion compounds demonstrated changes in the size of the ABA/βCD HNP if compared with the ABA HNP. Finally, the results for biological assays demonstrate that the strategy to prepare the inclusion compound led to an increase in the larvicidal activity in relation to free ABA.

The ofloxacin (OFLOX) is a second-generation synthetic antibiotic that can be classified as a multifunctional drug, but is a poorly soluble drug, which influences its efficiency. The inclusion complexes of OFLOX with β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) can improve the chemical characteristics of the drug; however, studies showing the biological activity of these inclusion complexes are still scarce. The present work aimed to investigate the multifunctionality of the OFLOX and their inclusion complexes. Thus, the 1:1 βCD/OFLOX or HPβCD/OFLOX were prepared and analyzed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric and differential thermal analysis (TGA and DTA), 1H nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). The antitumor and antibacterial effects were assessed. The results confirm the formation of the inclusion complexes, which had lower minimum inhibitory concentration (MIC) values, higher cytotoxicity and promoted the apoptosis. The present study showed, for the first time, the promising effects of the inclusion complexes as antitumor, improving the biological activities of the uncomplexed ofloxacin.