Related Experiment Video
Updated: Aug 16, 2025

Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine
Published on: October 11, 2019
Preparation, biological evaluation and QSAR analysis of urea substituted 2,4-diamino-pyrimidine anti-malarials
Borvornwat Toviwek1,2, Jennifer Riley3, Nicole Mutter3
1Department of Biomedical Engineering, School of Engineering, King Mongkut's Institute of Technology Ladkrabang Bangkok 10520 Thailand paul.gl@kmitl.ac.th.
Abstract:
The synthesis and evaluation of twenty six new phenylurea substituted 2,4-diamino-pyrimidines against Plasmodium falciparum (Pf) 3D7 are reported. Compounds were prepared to improve both anti-malarial activity and selectivity of the series previously reported by our group. Additional properties have been determined to assess their potential as anti-malarial leads including; HepG2 cytotoxicity, solubility, permeability, and lipophilicity, as well as in vitro stability in human and rat microsomes. We also assess their inhibition profile against a diverse set of 10 human kinases. Molecular docking, cheminformatics and bioinformatics analyses were also undertaken. Compounds 40 demonstrated the best anti-malarial activity at Pf 3D7 (0.09 μM), good selectivity with respect to mammalian cytotoxicity (SI = 54) and low microsomal clearance. Quantitative structure activity relationship (QSAR) analyses point to lipophilicity being a key driver of improved anti-malarial activity. The most active compounds in the series suffered from high lipophilicity, poor aqueous solubility and low permeability. The results provide useful information to guide further chemistry iterations.
Related Concept Videos
Physical Properties of Amines
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Aryldiazonium Salts to Azo Dyes: Diazo Coupling

