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Molecules 2014, 19(1), 367-399; doi:10.3390/molecules19010367
Article

A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity

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Received: 21 October 2013; in revised form: 19 November 2013 / Accepted: 19 November 2013 / Published: 30 December 2013
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Abstract: The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor (heme). Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE), the charge on the O11 oxygen atom (QO11), the torsion angle O1-O2-Fe-N2 (D2) and the maximum rate of R/Sanderson Electronegativity (RTe+). These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents.
Keywords: artemisinin; antimalarial activity; HF/6-31G**; molecular docking; MEPs; SAR; QSAR artemisinin; antimalarial activity; HF/6-31G**; molecular docking; MEPs; SAR; QSAR
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.

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MDPI and ACS Style

Santos, C.B.R.; Vieira, J.B.; Lobato, C.C.; Hage-Melim, L.I.S.; Souto, R.N.P.; Lima, C.S.; Costa, E.V.M.; Brasil, D.S.B.; Macêdo, W.J.C.; Carvalho, J.C.T. A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity. Molecules 2014, 19, 367-399.

AMA Style

Santos CBR, Vieira JB, Lobato CC, Hage-Melim LIS, Souto RNP, Lima CS, Costa EVM, Brasil DSB, Macêdo WJC, Carvalho JCT. A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity. Molecules. 2014; 19(1):367-399.

Chicago/Turabian Style

Santos, Cleydson B.R.; Vieira, Josinete B.; Lobato, Cleison C.; Hage-Melim, Lorane I.S.; Souto, Raimundo N.P.; Lima, Clarissa S.; Costa, Elizabeth V.M.; Brasil, Davi S.B.; Macêdo, Williams J.C.; Carvalho, José C.T. 2014. "A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity." Molecules 19, no. 1: 367-399.



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