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Molecular Docking and QSAR Study of Chalcone and Pyrimidine Derivatives as Potent Anti-Malarial Agents against Plasmodium falciparum

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A data set of chalcone and pyrimidine derivatives with anti-malarial activity against Plasmodium falciparum was employed in investigating the quantitative structure-activity relationship (QSAR). Molecular docking study was performed for plasmodium falciparum dihydrofolate reductase (PfDHFR-TS). Genetic function approximation (GFA) technique was used to identify the descriptors that have influence on anti-malarial activity. The most influencing molecular descriptors identified include thermodynamics, structural and physical descriptors. Generated model was found to be good based on correlation coefficient, LOF, rm2 and rcv2 values. Nrotb, solubility, polarizibility may have negative influence on antimalarial activity or play an important role in growth inhibition of Plasmodium falciparum. The QSAR models so constructed provide fruitful insights for the future development of anti-malarial agents.


International Letters of Chemistry, Physics and Astronomy (Volume 85)
D. J. Christian et al., "Molecular Docking and QSAR Study of Chalcone and Pyrimidine Derivatives as Potent Anti-Malarial Agents against Plasmodium falciparum", International Letters of Chemistry, Physics and Astronomy, Vol. 85, pp. 23-34, 2020
Online since:
December 2020

[1] World Health Organisation, (2013) World Malaria Report.

[2] P.K. Chiang et al., Malaria: therapy, genes and vaccines, Curr. Mol. Med. 6 (2006) 309-326.

[3] M.J. Gardner et al., Genome sequence of the human malaria parasite Plasmodium falciparum, Nature 419 (2002) 498-511.

[4] L. Florens et al., A proteomic view of the Plasmodium falciparum life cycle, Nature 419 (2002) 520-526.

[5] T. Lemcke, I.T. Christensen, F.S. Jorgensen, Towards an understanding of drug resistance in malaria: three-dimensional structure of Plasmodium falciparum dihydrofolate reductase by homology building, Bioorg. med. chem. 7 (1999) 1003-1011.


[6] G. Rastelli et al., Interaction of pyrimethamine, cycloguanil, WR99210 and their analogues with Plasmodium falciparum dihydrofolate reductase: structural basis of antifolate resistance, Bioorg. med. chem. 8 (2000) 1117-1128.


[7] R.T. Delfino, O.A. Santos, J.D. Figueroa-Villar, Molecular modeling of wild-type and antifolate resistant mutant Plasmodium falciparum DHFR, Biophys. Chem. 98 (2002) 287-300.


[8] D.R. Knighton et al., Structure of and kinetic channelling in bifunctional dihydrofolate reductase–thymidylate synthase, Nat. Struct. Biol. 1 (1994) 186-194.


[9] A. Gregson, C.V. Plowe, Mechanisms of resistance of malaria parasites to antifolates, Pharmacol. Rev. 57 (2005) 117-145.


[10] I.M. Kompis, K. Islam, R.L. Then, DNA and RNA synthesis: antifolates, Chem. Rev. 105 (2005) 593-620.

[11] D.J. Christian et al., Microwave Assisted Synthesis and in Vitro Anti-malarial Screening of Novel Pyrimidine Derivatives, World J. Pharma. Pharma Sci. 3 (2014) 1955-1971.

[12] J.M. Beierlein, N.G. Karri, A.C. Anderson, Targeted Mutations of Bacillus anthracis Dihydrofolate Reductase Condense Complex Structure− Activity Relationships, J. Med. Chem. 53 (2010) 7327-7336.


[13] A.T.R. Laurie, R.M. Jackson, Q-SiteFinder: an energy-based method for the prediction of protein–ligand binding sites, Bioinformatic 21 (2005) 1908-1916.


[14] L.K. Wolf, Quidditch For Chemists, ChemEng News Arch 87 (2009) 48-48.

[15] G.N. Ramachandran, C. Ramakrishnan, V. Sasisekharan, Conformation of polypeptides and proteins, J. Mol. Biol. 7 (1963) 95-99.

[16] P. Benkert, S.C.E. Tosatto, D. Schomburg, QMEAN: A comprehensive scoring function for model quality assessment, Proteins Struct. Funct. Bioinf. 71 (2008) 261-277.


[17] S.F. Altschul et al., Basic local alignment search tool, J. Mol. Biol. 215 (1990) 403-410.


[19] I.A. Khan et al., Quantitative structure–activity relationship (QSAR) of aryl alkenyl amides/imines for bacterial efflux pump inhibitors, Eur. J. Med. Chem. 44 (2009) 229-238.


[20] S. Peterangelo, P. Seybold, Synergistic interactions among QSAR descriptors, Int. J. Quantum Chem. 96 (2004) 1-9.


[21] S. Kulkarni, V.M. Kulkarni, Three-Dimensional Quantitative Structure-Activity Relationship of Interleukin 1-β Converting Enzyme Inhibitors: A Comparative Molecular Field Analysis Study, J. Med. Chem. 42 (1999) 373-380.


[22] P. Roy, K. Roy, On some aspects of variable selection for partial least squares regression models, QSAR Comb. Sci. 27 (2007) 302-313.

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