Optimisation of 2-(N-Phenyl Carboxamide) Triazolopyrimidine Antimalarials with Moderate to Slow Acting Erythrocytic Stage Activity

2021 ◽  
pp. 105244
Author(s):  
Brodie L. Bailey ◽  
William Nguyen ◽  
Anna Ngo ◽  
Christopher D. Goodman ◽  
Maria R. Gancheva ◽  
...  
Keyword(s):  
2015 ◽  
Vol 290 (49) ◽  
pp. 29629-29641 ◽  
Author(s):  
Boniface M. Mailu ◽  
Ling Li ◽  
Jen Arthur ◽  
Todd M. Nelson ◽  
Gowthaman Ramasamy ◽  
...  
Keyword(s):  

2017 ◽  
Vol 8 ◽  
Author(s):  
Rani Soni ◽  
Drista Sharma ◽  
Praveen Rai ◽  
Bhaskar Sharma ◽  
Tarun K. Bhatt

BMJ ◽  
1948 ◽  
Vol 1 (4550) ◽  
pp. 547-547 ◽  
Author(s):  
H. E. Shortt ◽  
P. C. C. Garnham ◽  
G. Covell ◽  
P. G. Shute

2009 ◽  
Vol 121 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Anusha M. Gopalakrishnan ◽  
Lilian A. Nyindodo ◽  
M. Ross Fergus ◽  
Carlos López-Estraño

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4376
Author(s):  
Marina Marinović ◽  
Ivana Perković ◽  
Diana Fontinha ◽  
Miguel Prudêncio ◽  
Jana Held ◽  
...  

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.


2000 ◽  
Vol 165 (2) ◽  
pp. 1123-1137 ◽  
Author(s):  
Denise L. Doolan ◽  
Scott Southwood ◽  
Robert Chesnut ◽  
Ettore Appella ◽  
Eduardo Gomez ◽  
...  

Parasitology ◽  
1967 ◽  
Vol 57 (2) ◽  
pp. 251-261 ◽  
Author(s):  
W. E. Stehbens ◽  
M. R. L. Johnston

The ultrastructure of the intra-erythrocytic stage of a haemogregarine in the gecko, Gehyra variegata, has been studied and numerous points of similarity to Plasmodium, Toxoplasma, Sarcocystis, Lankesterella, Eimeria and the M-organism were found. The protozoon was invested by a triple-layered pellicle, and possessed at least two micropyles. A conoid and apical rings were observed at the anterior end. Other cell constituents included nucleus, microtubules, endoplasmic reticulum, mitochondria, toxonemes and a variety of vacuoles. Loosely surrounding the parasite was an unusual convoluted membrane, which in appropriate planes of section, displayed corrugations on both surfaces. It was not clear whether this membranous structure should be regarded as an integral part of the protozoon or as an external coat which could be discarded upon emergence from the host red cell. Within its external sheath, the parasite lay in a periparasitic vacuole which was limited by a conventional unit membrane from the host red cell cytoplasm. The parasite did not exhibit any evidence of pinocytosis or phagocytosis.Our sincere thanks are due to Dr E. H. Mercer, Professor J. D. Smyth and Dr M. J. Mackerras for advice. Miss N. Carroll gave technical assistance.


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