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

Molecules

Cleydson Breno R. Santos¹  Josinete B. Vieira¹  Cleison C. Lobato¹  Lorane I. S. Hage-Melim¹  Raimundo N. P. Souto⁴  Clarissa S. Lima³  Elizabeth V. M. Costa³  Davi S. B. Brasil²  Williams Jorge C. Macອo¹ 

[1] Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil; E-Mails:;Institute of Technology, Federal University of Pará, Av. Augusto Corrêa, 01, Belém 66075-900, Pará, Amazon, Brazil; E-Mail:;Laboratory of Drug Research, School of Pharmaceutical Sciences, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil; E-Mails:;Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Macapá 68902-280, Amapá, Amazon, Brazil; E-Mails:

关键词: artemisinin;    antimalarial activity;    HF/6-31G**;    molecular docking;    MEPs;    SAR;    QSAR;   

DOI  :  10.3390/molecules19010367

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.