7H‐Pyrrolo[2, 3‐d]pyrimidine‐4‐amines as Potential Inhibitors of Plasmodium falciparum Calcium‐Dependent Protein Kinases. (29th September 2022)

• Record Type: Journal Article
• Authors: Seanego, Tswene D.; Chavalala, Hlamulo E.; Henning, Hendrik H.; de Koning, Charles B.; Hoppe, Heinrich C.; Ojo, Kayode K.; Rousseau, Amanda L.
• Is Part Of: ChemMedChem. Volume 17:Number 22(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-29
• Subjects: biological activity -- calcium-dependent protein kinases -- nitrogen heterocycles -- Plasmodium falciparum -- pyrrolo[2, 3-d]pyrimidine; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202200421
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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 (IC50 =0.210–0.530 μM), or Pf CDPK1 (IC50 =0.589 μM). These data will enable optimisation of the molecular model to better predict inhibitory activity against Pf CDPK4. Abstract : Hitting malaria where it hurts : Pyrrolo[2, 3‐ d ]pyrimidines have been designed as potential inhibitors targeting Plasmodium falciparum calcium‐dependent protein kinase 4 ( Pf CDPK4) using molecular modelling. Compounds displaying good binding interactions in silico were synthesised and assessed for inhibitory activity against Pf CDPK4 and Pf CDPK1, with several compounds displaying promising inhibitory activity against either Pf CDPK4 (IC50 =0.210–0.530 μM), or Pf CDPK1 (IC50 =0.589 μM).