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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity
|
|---|---|
| Published in |
Nature Microbiology, August 2017
|
| DOI | 10.1038/s41564-017-0007-4 |
| Pubmed ID | |
| Authors |
Manu Vanaerschot, Leonardo Lucantoni, Tao Li, Jill M. Combrinck, Andrea Ruecker, T. R. Santha Kumar, Kelly Rubiano, Pedro E. Ferreira, Giulia Siciliano, Sonia Gulati, Philipp P. Henrich, Caroline L. Ng, James M. Murithi, Victoria C. Corey, Sandra Duffy, Ori J. Lieberman, M. Isabel Veiga, Robert E. Sinden, Pietro Alano, Michael J. Delves, Kim Lee Sim, Elizabeth A. Winzeler, Timothy J. Egan, Stephen L. Hoffman, Vicky M. Avery, David A. Fidock |
| Abstract |
Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.A new class of drugs, hexahydroquinolines, inhibits host haemoglobin endocytosis by Plasmodium falciparum and displays both therapeutic and transmission-blocking activities. |
X Demographics
The data shown below were collected from the profiles of 19 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 3 | 16% |
| United States | 2 | 11% |
| Japan | 1 | 5% |
| France | 1 | 5% |
| Unknown | 12 | 63% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 47% |
| Scientists | 5 | 26% |
| Science communicators (journalists, bloggers, editors) | 3 | 16% |
| Practitioners (doctors, other healthcare professionals) | 2 | 11% |
Mendeley readers
The data shown below were compiled from readership statistics for 110 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 110 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 25 | 23% |
| Student > Ph. D. Student | 17 | 15% |
| Student > Master | 14 | 13% |
| Student > Bachelor | 9 | 8% |
| Other | 9 | 8% |
| Other | 9 | 8% |
| Unknown | 27 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 21 | 19% |
| Agricultural and Biological Sciences | 14 | 13% |
| Chemistry | 12 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 10 | 9% |
| Immunology and Microbiology | 6 | 5% |
| Other | 13 | 12% |
| Unknown | 34 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 67. 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 2018.
All research outputs
#618,865
of 24,823,556 outputs
Outputs from Nature Microbiology
#682
of 1,924 outputs
Outputs of similar age
#13,209
of 322,676 outputs
Outputs of similar age from Nature Microbiology
#24
of 52 outputs
Altmetric has tracked 24,823,556 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,924 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 95.4. This one has gotten more attention than average, scoring higher than 64% 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 322,676 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.