In vitro evaluation of 4-phenyl-5-(4'-X-phenyl)-1,3,4-thiadiazolium-2-phenylaminide chlorides and 3[N-4'-X-phenyl]-1,2,3-oxadiazolium-5-olate derivatives on nitric oxide synthase and arginase activities of Leishmania amazonensis.

Leishmaniasis is a spectrum of infectious diseases caused by Leishmania protozoan parasites. The purpose of this study was to perform, in vitro, a comparative analysis of the activity amastigotes. Results showed excellent efficacy of all compounds against axenic amastigotes, compared to pentamidine isethionate, the reference drug used. The cytotoxic effect of these mesoionic compounds of six mesoionic compounds (three 1,3,4-thiadiazolium-2-aminide and three 1,2,3-oxadiazolium-5-olate class compounds) was evaluated in mouse peritoneal macrophages using MTT assay, low toxicity (≈ 10%) for these mammalian cells being observed. In an attempt to define a potential drug target, the activities of nitric oxide synthase (NOS) and arginase of the parasites treated with the mesoionic derivatives were evaluated. NOS was purified from a cell-free extract of infective promastigotes and axenic amastigotes and all derivatives tested were able to inhibit the enzyme as monitored by the decrease of NADPH consumption. Arginase activity from both stages of the parasite was measured using urea production and none of the compounds inhibited the enzyme activity of axenic amastigotes. However, the compounds without substituents (MI-H and SID-H) were able to inhibit arginase activity of these parasites.

Green synthesis of silver nanoparticles combined to calcium glycerophosphate: antimicrobial and antibiofilm activities.

AIM: To synthesize, characterize and evaluate the antimicrobial and antibiofilm activities of novel nanocomposites containing silver nanoparticles (AgNPs) associated or not to ß-calcium glycerophosphate. MATERIALS & METHODS: These nanocomposites were produced through a 'green' route using extracts of different parts of pomegranate. Antimicrobial and antibiofilm properties against Candida albicans and Streptococcus mutans were determined by the minimum bactericidal/fungicidal concentration and biofilm density after treatments. RESULTS: All extracts used were successful in producing AgNPs. Composites made with peel extracts showed the highest antimicrobial and antibiofilm activity against both microorganisms tested and performed similarly or even better than chlorhexidine. CONCLUSION: AgNPs associated or not to calcium glycerophosphate produced by a 'green' process may be a promising novel antimicrobial agent against oral microorganisms.

Design, Synthesis, and Pharmacological Evaluation of Novel N-Acylhydrazone Derivatives as Potent Histone Deacetylase 6/8 Dual Inhibitors.

This manuscript describes a novel class of N-acylhydrazone (NAH) derivatives that act as histone deacetylase (HDAC) 6/8 dual inhibitors and were designed from the structure of trichostatin A (1). Para-substituted phenyl-hydroxamic acids presented a more potent inhibition of HDAC6/8 than their meta analogs. In addition, the effect of compounds (E)-4-((2-(4-(dimethylamino)benzoyl)hydrazono)methyl)-N-hydroxybenzamide (3c) and (E)-4-((2-(4-(dimethylamino)benzoyl)-2-methylhydrazono)methyl)-N-hydroxybenzamide (3f) on the acetylation of α-tubulin revealed an increased level of acetylation. These two compounds also affected cell migration, indicating their inhibition of HDAC6. An analysis of the antiproliferative activity of these compounds, which presented the most potent activity, showed that compound 3c induced cell cycle arrest and 3g induced apoptosis through caspase 3/7 activation. These results suggest HDAC6/8 as a potential target of future molecular therapies for cancer.