Title |
Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi
|
---|---|
Published in |
Future Medicinal Chemistry, January 2018
|
DOI | 10.4155/fmc-2017-0184 |
Pubmed ID | |
Authors |
Ligia F Ceole, Hirenkumar Gandhi, Luz H Villamizar, Maurilio J Soares, Timothy P O'Sullivan |
Abstract |
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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Ireland | 2 | 40% |
United States | 1 | 20% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 60% |
Scientists | 2 | 40% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 18 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 7 | 39% |
Student > Bachelor | 1 | 6% |
Other | 1 | 6% |
Student > Ph. D. Student | 1 | 6% |
Student > Postgraduate | 1 | 6% |
Other | 0 | 0% |
Unknown | 7 | 39% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 5 | 28% |
Biochemistry, Genetics and Molecular Biology | 3 | 17% |
Agricultural and Biological Sciences | 2 | 11% |
Immunology and Microbiology | 1 | 6% |
Design | 1 | 6% |
Other | 0 | 0% |
Unknown | 6 | 33% |