Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives

Kulatee, Suriyawut; Toochinda, Pisanu; Suksangpanomrung, Anotai; Lawtrakul, Luckhana

doi:10.3390/scipharm85040037

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Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives

Suriyawut Kulatee

¹,

Pisanu Toochinda

¹,

Anotai Suksangpanomrung

² and

Luckhana Lawtrakul

^1,*

School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand

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

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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

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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. https://doi.org/10.3390/scipharm85040037

AMA Style

Kulatee S, Toochinda P, Suksangpanomrung A, Lawtrakul L. Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives. Scientia Pharmaceutica. 2017; 85(4):37. https://doi.org/10.3390/scipharm85040037

Chicago/Turabian Style

Kulatee, Suriyawut, Pisanu Toochinda, Anotai Suksangpanomrung, and Luckhana Lawtrakul. 2017. "Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives" Scientia Pharmaceutica 85, no. 4: 37. https://doi.org/10.3390/scipharm85040037

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Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives

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