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
Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.
Subject(s)
Aedes/drug effects , Insecticides/pharmacology , Phenols/pharmacology , Animals , Insecticides/chemical synthesis , Insecticides/toxicity , Larva/drug effects , Lethal Dose 50 , Phenols/chemistry , Phenols/isolation & purification , Phenols/toxicity , Time FactorsABSTRACT
ABSTRACT Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.
Subject(s)
Animals , Phenols/pharmacology , Aedes/drug effects , Insecticides/pharmacology , Phenols/isolation & purification , Phenols/toxicity , Phenols/chemistry , Time Factors , Insecticides/chemical synthesis , Insecticides/toxicity , Larva/drug effects , Lethal Dose 50ABSTRACT
Cytotoxic activity of eight plant extracts, native from the Mid-West of Brazil comprising Cerrado, Pantanal and semideciduous forest, was evaluated for MDA-MB-435, SF-295, and HCT-8 cancer cell strains. A single 100 µg.mL-1 dose of each extract was employed with 72 h of incubation for all tests. Doxorubicin (1 µg.mL-1) was used as the positive control and the MTT method was used to detect the activity. Cytotoxicity of distinct polarities was observed in thirty extracts (46 percent), from different parts of the following species: Tabebuia heptaphylla (Vell.) Toledo, Bignoniaceae, Tapirira guianensis Aubl., Anacardiaceae, Myracrodruon urundeuva Allemão, Anacardiaceae, Schinus terebinthifolius Raddi, Anacardiaceae, Gomphrena elegans Mart., Amaranthaceae, Attalea phalerata Mart. ex Spreng., Arecaceae, Eugenia uniflora L., Myrtaceae, and Annona dioica A. St.-Hil., Annonaceae. Extracts of at least two tested cell strains were considered to be highly active since their inhibition rate was over 75 percent.
