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

Clinton G L Veale; Janeeka Jayram; Shivani Naidoo; Dustin Laming; Tarryn Swart; Tania Olivier; Matthew P Akerman; Katherine A de Villiers; Heinrich C Hoppe; Vineet Jeena

doi:10.1039/c9md00468h

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

RSC Med Chem. 2019 Dec 16;11(1):85-91. doi: 10.1039/c9md00468h. eCollection 2020 Jan 1.

Affiliations

¹ School of Chemistry and Physics , Pietermaritzburg Campus , University of KwaZulu-Natal , Private Bag X01 , Scottsville , 3209 , South Africa.
² Department of Biochemistry and Microbiology , Rhodes University , Grahamstown , 6140 , South Africa.
³ Department of Chemistry and Polymer Science , Stellenbosch University , Private Bag X1 , Matieland , 7602 , South Africa . Email: VealeC@ukzn.ac.za ; Email: JeenaV1@ukzn.ac.za.

Abstract

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.