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Open AccessArticle

Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives

1
School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand
2
Department of Mechanical Engineering, Academic Division, Chulachomklao Royal Military Academy, Nakhon Nayok 26001, Thailand
*
Author to whom correspondence should be addressed.
Academic Editor: Gernot A. Eller
Sci. Pharm. 2017, 85(4), 37; https://doi.org/10.3390/scipharm85040037
Received: 20 September 2017 / Revised: 10 November 2017 / Accepted: 14 November 2017 / Published: 21 November 2017
Point mutations in Plasmodium falciparum dihydrofolate reductase (pfDHFR), especially the double mutant variant (A16V + S108T), led to ineffective inhibiting by cycloguanil (Cyc). Cycloguanil derivatives showed good inhibiting properties against wild-type and mutant pfDHFR with an inhibition constant as low as the nanomolar level. However, there have been no reports on the stereochemistry of the compounds, and this is important because the pure enantiomeric form of a chiral drug can exert desirable, as well as non-desirable responses on the body or both. In this work, three-dimensional structures of Cyc derivatives in R and S configuration were constructed and optimized using Hartree-Fock/6-31G (d,p). Their structures were docked into the binding pocket of wild-type and double mutant (A16V + S108T) pfDHFR, complexed with nicotinamide adenine dinucleotide phosphate (NADPH). Results indicate that both wild-type and mutant pfDHFR are enantioselective towards enantiomeric Cyc derivatives (R and S configuration). View Full-Text
Keywords: antimalarial drugs; cycloguanil enantiomers; molecular docking; protein–ligand interaction antimalarial drugs; cycloguanil enantiomers; molecular docking; protein–ligand interaction
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Kulatee, S.; Toochinda, P.; Suksangpanomrung, A.; Lawtrakul, L. Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives. Sci. Pharm. 2017, 85, 37.

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