Back to Search
Start Over
Synthesis and in vitro evaluation of tropane halogenated-derivatives against malaria, sleeping sickness, Chagas disease and leishmaniasis.
Synthesis and in vitro evaluation of tropane halogenated-derivatives against malaria, sleeping sickness, Chagas disease and leishmaniasis.
- Source :
-
Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2014; Vol. 10 (8), pp. 753-8. - Publication Year :
- 2014
-
Abstract
- A series of twelve analogs carrying fluoro, chloro, bromo and iodo halogens on the ortho, meta and para positions of a benzoyloxytropane skeleton were synthesized by a simple acylation of 8-methyl-8-aza-bicyclo[3.2.1]octan- 3α-ol by halogenobenzoyl chlorides. The compounds were evaluated in vitro against Plasmodium falciparum (P. f.), Trypanosoma brucei brucei (T. b. b.), Trypanosoma cruzi (T. c.) and Leishmania infantum (L. i.). This study shows that the presence of a halogenated atom and its position on the aromatic ring are important for in vitro activity. Compounds 4 (IC50 = 3.6 µM), 8 (IC50 = 6.7 µM), 5 (IC50 = 8.1 µM) and 7 (IC50 = 9.5 µM) were found the most active against P. f., whereas compounds 12 (IC50 = 5.1 µM), 11 (IC50 = 5.6 µM) and 9 (IC50 = 5.8 µM) exhibited the most pronounced activity against T. b. b. This series of compounds can be considered as non-toxic to the human cell line MRC-5.
- Subjects :
- Acylation
Animals
Antimalarials chemistry
Antimalarials pharmacology
Antiprotozoal Agents chemistry
Antiprotozoal Agents pharmacology
Cells, Cultured
Cricetinae
Erythrocytes drug effects
Erythrocytes parasitology
Fibroblasts drug effects
Fibroblasts parasitology
Halogenation
Humans
Inhibitory Concentration 50
Leishmania infantum drug effects
Leishmania infantum growth & development
Macrophages, Peritoneal drug effects
Macrophages, Peritoneal parasitology
Mice
Parasitic Sensitivity Tests
Plasmodium falciparum drug effects
Plasmodium falciparum growth & development
Structure-Activity Relationship
Tropanes chemistry
Tropanes pharmacology
Trypanocidal Agents chemistry
Trypanocidal Agents pharmacology
Trypanosoma brucei brucei drug effects
Trypanosoma brucei brucei growth & development
Trypanosoma cruzi drug effects
Trypanosoma cruzi growth & development
Antimalarials chemical synthesis
Antiprotozoal Agents chemical synthesis
Tropanes chemical synthesis
Trypanocidal Agents chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1875-6638
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Medicinal chemistry (Shariqah (United Arab Emirates))
- Publication Type :
- Academic Journal
- Accession number :
- 24813684
- Full Text :
- https://doi.org/10.2174/1573406410666140507095430