Antimicrobial activity of nanoparticles based on carboxymethylated cashew gum and epiisopiloturine: In vitro and in silico studies.

Epiisopiloturine (EPI) is a compound found in jaborandi leaves with antiparasitic activity, which can be enhanced when incorporated into nanoparticles (NP). Cashew Gum (CG), modified by carboxymethylation, is used to produce polymeric nanomaterials with biological activity. In this study, we investigated the antimicrobial potential of carboxymethylated CG (CCG) NP containing EPI (NPCCGE) and without the alkaloid (NPCCG) against bacteria and parasites of the genus Leishmania. We conducted theoretical studies, carboxymethylated CG, synthesized NP by nanoprecipitation, characterized them, and tested them in vitro. Theoretical studies confirmed the stability of modified carbohydrates and showed that the EPI-4A30 complex had the best interaction energy (-8.47 kcal/mol). CCG was confirmed by FT-IR and presented DSabs of 0.23. NPCCG and NPCCGE had average sizes of 221.94 ± 144.086 nm and 247.36 ± 3.827 nm, respectively, with homogeneous distribution and uniform surfaces. No NP showed antibacterial activity or cytotoxicity to macrophages. NPCCGE demonstrated antileishmanial activity against L. amazonensis, both in promastigote forms (IC50 = 9.52 µg/mL, SI = 42.01) and axenic amastigote forms (EC50 = 6.6 µg/mL, SI = 60.60). The results suggest that nanostructuring EPI in CCG enhances its antileishmanial activity.

Sulfonamide-chalcone hybrid compound suppresses cellular adhesion and migration: Experimental and computational insight.

In the present study, the effect of sulfonamide-chalcone 185 (SSC185) was investigated against B16-F10 metastatic melanoma cells aggressive actions, besides migration and adhesion processes, by in silico and in vitro assays. In silico studies were used to characterize the pharmacokinetic profile and possible targets of SSC185, using the pkCSM web server, and docking simulations with AutoDock Tools. Furthermore, the antimetastatic effect of SSC185 was investigated by in vitro experiments using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony, scratch, and cell adhesion assays, and atomic force microscopy (AFM). The molecular docking results show better affinity of SSC185 with the metalloproteinases-2 (MMP-2) and α5ß1 integrin. SSC185 effectively restricts the formation of colonies, migration, and adhesion of B16-F10 metastatic melanoma cells. Through the AFM images changes in cells morphology was identified, with a decrease in the filopodia and increase in the average cellular roughness. The results obtained demonstrate the potential of this molecule in inhibit the primordial steps for metastasis, which is responsible for a worse prognosis of late stage cancer, being the main cause of morbidity among cancer patients.

Cytotoxic and Antileishmanial Effects of the Monoterpene ß-Ocimene.

Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. ß-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of ß-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. ß-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 µM) and axenic amastigotes (EC50 = 1.12 µM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. ß-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 µM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that ß-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.

Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.

Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In previous works we have demonstrated the effective and selective antileishmanial activity of Eugenia uniflora L. essential oil, being constituted (47.3%) by the sesquiterpene curzerene. Considering the high rate of parasite inhibition demonstrated for E. uniflora essential oil, and the significant presence of curzerene in the oil, this study aimed to evaluate its antileishmania activity and possible mechanisms of action. Curzerene was effective in inhibiting the growth of promastigotes (IC50 3.09 ± 0.14 µM) and axenic amastigotes (EC50 2.56 ± 0.12 µM), with low cytotoxicity to RAW 264.7 macrophages (CC50 83.87 ± 4.63 µM). It was observed that curzerene has direct effects on the parasite, inducing cell death by apoptosis with secondary necrotic effects (producing pores in the plasma membrane). Curzerene proved to be even more effective against intra-macrophage amastigote forms, with an EC50 of 0.46 ± 0.02 µM. The selectivity index demonstrated by curzerene on these parasite forms was 182.32, being respectively 44.15 and 8.47 times more selective than meglumine antimoniate and amphotericin B. The antiamastigote activity of curzerene was associated with immunomodulatory activity, as it increased TNF-α, IL-12, and NO levels, and lysosomal activity, and decreased IL-10 and IL-6 cytokine levels detected in macrophages infected and treated. In conclusion, our results demonstrate that curzerene is an effective and selective antileishmanial agent, a candidate for in vivo investigation in models of antileishmanial activity.