Abstract
A quantitative structure-activity relationship (QSAR) study was conducted using nineteen previously synthesized, and tested 1-aryl-6-hydroxy-1,2,3,4-tetrahydroisoquinolines with proven in vitro activities against Plasmodium falciparum. In order to computationally design and screen potent antimalarial agents, these compounds with known biological activity ranging from 0.697 to 35.978 μM were geometry optimized at the B3LYP/6-311 + G(d,p) level of theory, using the Gaussian 09W software. To calculate the topological differences, the series of the nineteen compounds was superimposed and a hypermolecule obtained with s ¯ = 17 and 20 vertices. Other molecular descriptors were considered in order to build a highly predictive QSAR model. These include the minimal topological differences (MTD), LogP, two dimensional polarity surface area (TDPSA), dipole moment (μ), chemical hardness (η), electrophilicity (ω), potential energy (Ep), electrostatic energy (Eele) and number of rotatable bonds (NRB). By using a training set composed of 15 randomly selected compounds from this series, several QSAR equations were derived. The QSAR equations obtained were then used to attempt to predict the IC50 values of 4 remaining compounds in a test (or...Continue Reading
References
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Jan 15, 1988·Physical Review. B, Condensed Matter·C LeeR G Parr
Feb 8, 2002·Nature·Robert G Ridley
Aug 22, 2003·Journal of Medicinal Chemistry·Cassandra L WoodardNorman C Waters
Jun 9, 2004·Journal of Computational Chemistry·Kenneth B Wiberg
Jul 28, 2005·Journal of Molecular Graphics & Modelling·Youyi PengWilliam J Welsh
Dec 17, 2005·European Journal of Medicinal Chemistry·Arun KumarPrem M S Chauhan
May 16, 2006·Medicinal Research Reviews·Suryanaryana VangapanduRahul Jain
May 4, 2007·European Journal of Medicinal Chemistry·Gerhard BringmannStefan Neumann
Feb 17, 2009·European Journal of Medicinal Chemistry·Vladimir FrecerStanislav Miertus
Mar 9, 2010·European Journal of Medicinal Chemistry·Ravi KumarPrem M S Chauhan
Mar 7, 2013·Biochimica Et Biophysica Acta·Teresa Gil CarvalhoLuc Reininger
Dec 18, 2013·Malaria Journal·Pascal Amoa OnguénéLuc Meva'a Mbaze
Mar 8, 2014·Malaria Journal·Fidele Ntie-KangLuc Meva'a Mbaze
Jan 26, 2017·Journal of Natural Products·Jun LiGerhard Bringmann
Mar 16, 2017·Cold Spring Harbor Perspectives in Medicine·Didier Menard, Arjen Dondorp
Nov 13, 2018·Fitoterapia·Shaimaa FayezGerhard Bringmann
May 20, 2020·Malaria Journal·Boris D BekonoLuc C O Owono
Jun 3, 2020·Scientific Reports·Mamadou Alpha DialloDaouda Ndiaye
Jun 7, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Phanankosi MoyoLyn-Marie Birkholtz