Insights into structural and physicochemical properties required for β-hematin inhibition of privileged triarylimidazoles

In this study, we investigated a series of triarylimidazoles, in an effort to elucidate critical SAR information pertaining to their anti-plasmodial and β-hematin inhibitory activity. Our results showed that in addition to the positional effects of ring substitution, subtle changes to lipophilicity...

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Bibliographic Details
Published in:MedChemComm 2020-01, Vol.11 (1), p.85-91
Main Authors: Veale, Clinton G. L, Jayram, Janeeka, Naidoo, Shivani, Laming, Dustin, Swart, Tarryn, Olivier, Tania, Akerman, Matthew P, de Villiers, Katherine A, Hoppe, Heinrich C, Jeena, Vineet
Format: Article
Language:English
Subjects:
Chemistry
Crystal growth
Imidazole
Lipophilicity
Physicochemical properties
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Summary:In this study, we investigated a series of triarylimidazoles, in an effort to elucidate critical SAR information pertaining to their anti-plasmodial and β-hematin inhibitory activity. Our results showed that in addition to the positional effects of ring substitution, subtle changes to lipophilicity and imidazole ionisability were important factors in SAR interpretation. Finally, in silico adsorption analysis indicated that these compounds exert their effect by inhibiting β-hematin crystal growth at the fast growing 001 face. In this study we provide deeper insight into both the structural and physicochemical properties of the privileged triarylimidazole required for inhibition of β-hematin formation.
ISSN:2632-8682
2040-2503
2632-8682
2040-2511
DOI:10.1039/c9md00468h