title: A SAR and QSAR study of new artemisinin compounds with antimalarial activity.
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.
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. breno@unifap.br.
authors.forename: Cleydson Breno R
authors.initials: CB
authors.lastname: Santos
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. jnetbio.unifap2011.ap@gmail.com.
authors.forename: Josinete B
authors.initials: JB
authors.lastname: Vieira
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. cleyson.cl@gmail.com.
authors.forename: Cleison C
authors.initials: CC
authors.lastname: Lobato
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. lorane@unifap.br.
authors.forename: Lorane I S
authors.initials: LI
authors.lastname: Hage-Melim
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. rnpsouto@unifap.br.
authors.forename: Raimundo N P
authors.initials: RN
authors.lastname: Souto
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. lima.clarissa@gmail.com.
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Lima
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. elizabethviana@unifap.br.
authors.forename: Elizabeth V M
authors.initials: EV
authors.lastname: Costa
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. davibb@ufpa.br.
authors.forename: Davi S B
authors.initials: DS
authors.lastname: Brasil
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. williamsmacedo@yahoo.com.br.
authors.forename: Williams Jorge C
authors.initials: WJ
authors.lastname: Macêdo
authors.affiliation: Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, Brazil. farmacos@unifap.br.
authors.forename: José Carlos T
authors.initials: JC
authors.lastname: Carvalho
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology*; D016000:Cluster Analysis; D006418:Heme / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006418:Heme; C031327:artemisinin