We have located links that may give you full text access.
Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor In Vivo Using Fluorinated Bisquinolines.
Chemistry : a European Journal 2017 May 18
Antimalarials can interact with heme covalently, by π⋅⋅⋅π interactions or by hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated by using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen because of electronic rather than steric factors. In gas-phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation, which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluoromethyl groups buttressing the quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/BS1) and crystal structure of (±)-trans-N1 ,N2 -bis-(2,8-ditrifluoromethylquinolin-4-yl)cyclohexane-1,2-diamine were used to reveal the preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III) state, which has important implications for the future rational design of 4-aminoquinoline antimalarials.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app