Next Article in Journal
A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations
Previous Article in Journal
Leishmanicidal Activity of Biogenic Fe3O4 Nanoparticles
Article Menu

Export Article

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
  |  
PDF [7390 KB, uploaded 22 November 2017]
  |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Kulatee, S.; Toochinda, P.; Suksangpanomrung, A.; Lawtrakul, L. Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives. Sci. Pharm. 2017, 85, 37.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Sci. Pharm. EISSN 2218-0532 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top