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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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
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Language:English
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Chemistry
Crystal growth
Imidazole
Lipophilicity
Physicochemical properties
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creator Veale, Clinton G. L
Jayram, Janeeka
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Hoppe, Heinrich C
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description 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.
doi_str_mv 10.1039/c9md00468h
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subjects Chemistry
Crystal growth
Imidazole
Lipophilicity
Physicochemical properties
title Insights into structural and physicochemical properties required for β-hematin inhibition of privileged triarylimidazoles
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