| Title |
Anti-trypanosomal activities and structural chemical properties of selected compound classes
|
|---|---|
| Published in |
Parasitology Research, November 2014
|
| DOI | 10.1007/s00436-014-4210-4 |
| Pubmed ID | |
| Authors |
Alicia Ponte-Sucre, Heike Bruhn, Tanja Schirmeister, Alexander Cecil, Christian R. Albert, Christian Buechold, Maximilian Tischer, Susanne Schlesinger, Tim Goebel, Antje Fuß, Daniela Mathein, Benjamin Merget, Christoph A. Sotriffer, August Stich, Georg Krohne, Markus Engstler, Gerhard Bringmann, Ulrike Holzgrabe |
| Abstract |
Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Denmark | 1 | 6% |
| Germany | 1 | 6% |
| Unknown | 16 | 89% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 39% |
| Lecturer | 1 | 6% |
| Student > Bachelor | 1 | 6% |
| Student > Doctoral Student | 1 | 6% |
| Student > Ph. D. Student | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 6 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 4 | 22% |
| Biochemistry, Genetics and Molecular Biology | 3 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 11% |
| Chemistry | 2 | 11% |
| Medicine and Dentistry | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 5 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 June 2016.
All research outputs
#7,204,207
of 22,771,140 outputs
Outputs from Parasitology Research
#570
of 3,781 outputs
Outputs of similar age
#102,630
of 361,726 outputs
Outputs of similar age from Parasitology Research
#11
of 86 outputs
Altmetric has tracked 22,771,140 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 3,781 research outputs from this source. They receive a mean Attention Score of 2.7. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 361,726 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 86 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.