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7 H ‐Pyrrolo[2,3‐ d ]pyrimidine‐4‐amines as Potential Inhibitors of Plasmodium falciparum Calcium‐Dependent Protein Kinases
Author(s) -
Seanego Tswene D.,
Chavalala Hlamulo E.,
Henning Hendrik H.,
Koning Charles B.,
Hoppe Heinrich C.,
Ojo Kayode K.,
Rousseau Amanda L.
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202200421
Subject(s) - in silico , kinase , plasmodium falciparum , in vitro , pyrimidine , inhibitory postsynaptic potential , biochemistry , chemistry , enzyme , stereochemistry , biology , gene , malaria , immunology , neuroscience
A series of pyrrolo[2,3‐ d ]pyrimidines were designed in silico as potential bumped kinase inhibitors targeting P. falciparum calcium dependent protein kinase 4 ( Pf CDPK4), with the potential to inhibit Pf CDPK1 based on earlier studies of the two kinases. A small series of these compounds were prepared and assessed for inhibitory activity against Pf CDPK4 and Pf CDPK1 in vitro . Four of the compounds displayed promising inhibitory activity against either Pf CDPK4 (IC 50 =0.210–0.530 μM), or Pf CDPK1 (IC 50 =0.589 μM). These data will enable optimisation of the molecular model to better predict inhibitory activity against Pf CDPK4.