As part of our medicinal chemistry program’s ongoing search for compounds with antimalarial activity, we prepared a series of thiazole analogs and conducted a SAR study analyzing their in vitro activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain.
Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer.
Click chemistry technique led to novel 1,2,3-triazole-quinine conjugates 8a–g, 10a–o, 11a–h and 13 utilizing benzotriazole-mediated synthetic approach with excellent yields.
Despite a decline in the prevalence of chloroquine resistance due to the official withdrawal of the drug and to the introduction of ACT, the spread of resistance to chloroquine has continued.
As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases.
Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7).
Improving women’s knowledge of malaria in pregnancy is not sufficient to assure adherence to anti-malarial treatment.
The study revealed the relative effectiveness of the technologies as quality control tools.
The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro.
Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease.