ABSTRACT
In pursuit of potential agents to treat Chagas disease and leishmaniasis, we report the design, synthesis, and identification novel naphthoquinone hydrazide-based molecular hybrids. The compounds were subjected to in vitro trypanocide and leishmanicidal activities. N'-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-3,5-dimethoxybenzohydrazide (13) showed the best performance against Trypanosoma cruzi (IC50 1.83 µM) and Leishmania amazonensis (IC50 9.65 µM). 4-Bromo-N'-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide (16) exhibited leishmanicidal activity (IC50 12.16 µM). Regarding trypanocide activity, compound 13 was low cytotoxic to LLC-MK2 cells (SI = 95.28). Furthermore, through molecular modeling studies, the cysteine proteases cruzain, rhodesain and CPB2.8 were identified as the potential biological targets.
Subject(s)
Drug Design , Hydrazines , Leishmania , Naphthoquinones , Trypanocidal Agents , Trypanosoma cruzi , Naphthoquinones/pharmacology , Naphthoquinones/chemistry , Naphthoquinones/chemical synthesis , Trypanosoma cruzi/drug effects , Trypanocidal Agents/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry , Leishmania/drug effects , Hydrazines/chemistry , Hydrazines/pharmacology , Animals , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Parasitic Sensitivity Tests , Inhibitory Concentration 50 , Structure-Activity Relationship , Cysteine EndopeptidasesABSTRACT
The objective of this study is to propose the use of specific synthetic lipid as an active substance (biocide) in the control of harmful aquatic microorganisms, such as pathogens and non-indigenous species, transported in ships' ballast water. The biocide candidate, without metal or halogen components, was produced from a sub-product of the edible oil industry, the lecithin. Laboratory assays were conducted with phytoplankton, zooplankton, and marine bacteria to evaluate the efficiency of the biocide. The study also considers specific biocide's characteristics related to environmental risks, such as chemical composition, persistence, bioaccumulation, and toxicity. Results showed that, in the first 24â¯h of treatment, the biocide effectively reduced the concentration of the planktonic micro-organisms to very low levels. Additionally, a preliminary risk evaluation pointed that biocide candidate has a low residual toxicity, also a low potential for persistence and bioaccumulation in the environment.
Subject(s)
Disinfectants/pharmacology , Lipids/pharmacology , Water Purification/methods , Bacteria/drug effects , Phytoplankton/drug effects , Plankton/drug effectsABSTRACT
The current work aimed to identify the source of an oil spill off the coast of Maranhão, Brazil, in September 2005 and effect a preliminary geochemical survey of this environment. A combination of bulk analytical parameters, such as carbon isotope (δ(13)C) and Ni/V ratios, and conventional fingerprinting methods (High Resolution Gas Chromatography and Mass Spectrometry) were used. The use of bulk methods greatly speeded source identification for this relatively unaltered spill: identification of the likely source was possible at this stage. Subsequent fingerprinting of biomarker distributions supported source assignment, pointing to a non-Brazilian oil. Steranes proved the most useful biomarkers for sample correlation in this work. Distribution patterns of environmentally more resilient compound types, such as certain aromatic structures, proved inconclusive for correlation, probably in view of their presence in the background.