ABSTRACT
AIM: Chagas disease is a tropical disease caused by the hemoflagellate protozoan Trypanosoma cruzi. There is no vaccine for Chagas disease and available drugs (e.g., benznidazole) are effective only during the acute phase, displaying a variable curative activity in the established chronic form of the disease. New leads with high efficacy and better toxicity profiles are urgently required. Materials & methods: A library of novel quinine derivatives was synthesized using Heck chemistry and evaluated against the various developmental forms of T. cruzi. RESULTS AND CONCLUSION: Several novel quinine analogs with trypanocidal activity have been identified with the para-nitro-substituted derivative displaying a submicromolar IC50, which is 83-times lower than quinine and three-times lower than benznidazole. Transmission electron microscopy analysis demonstrated that these compounds induced a marked vacuolization of the kinetoplast of intracellular amastigotes and cell-derived trypomastigotes.
Subject(s)
Chagas Disease/drug therapy , Chagas Disease/parasitology , Quinine/analogs & derivatives , Quinine/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Cell Survival/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Microscopy, Electron, Transmission , Molecular Conformation , Parasitic Sensitivity Tests , Quinine/chemical synthesis , Quinine/chemistry , Structure-Activity Relationship , Trypanocidal Agents/chemistry , Vero CellsABSTRACT
A sonar based device with tactile feedback was developed to improve the mobility and independence of visually impaired individuals. It features a transceiver/receiver, a potentiometer, a microcontroller, a rechargeable polymer lithium ion battery, and a Nokia Cell phone vibrator. All components are commercially available and housed in a custom acrylic package with 86 mm × 34 mm × 12 mm in dimension, and 120 grms in weight. Additionally, the device features an adjustable detection scheme for user customization of distance range, and a tactile feedback system that avoids interference with auditory sensory information. The device was tested for its navigational efficacy in an artificial indoor environment, and in a live outdoor setting. Ten subjects (9 males and 1 female), with a mean age of 35 years-old (range: 17 to 52) were presented with a series of navigational tasks resulting in considerable reduction of head, shoulder, chest, and arms collisions during their locomotion. We conclude that this device greatly improves the mobility and safety of visually impaired individuals.
