title: In silico analysis reveals the anti-malarial potential of quinolinyl chalcone derivatives.
abstract: In this study, the correlation between chemical structures and various parameters such as steric effects and electrostatic interactions to the inhibitory activities of quinolinyl chalcone derivatives is derived to identify the key structural elements required in the rational design of potent and novel anti-malarial compounds. The molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex-dock is used to determine the probable binding conformations of all the compounds at the active site of pfLDH and to identify the hydrogen bonding interactions which could be used to alter the inhibitory activities. The CoMFA model has provided statistically significant results with the cross-validated correlation coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number of component is five. The predictive ability of the resultant model is evaluated using a test set comprising of 13 molecules and the predicted r(2) value is .885. The results provide valuable insight for optimization of quinolinyl chalcone derivatives for better anti-malarial therapy.
authors.affiliation: a Medical & Biological Computing Laboratory, School of Biosciences and Technology , VIT University , Vellore 632 014 , Tamil Nadu , India.
authors.forename: Mahalakshmi
authors.initials: M
authors.lastname: Thillainayagam
authors.forename: Lavanya
authors.initials: L
authors.lastname: Pandian
authors.forename: Kumar Kalavathy
authors.initials: KK
authors.lastname: Murugan
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Vijayaparthasarathi
authors.forename: Sarveswari
authors.initials: S
authors.lastname: Sundaramoorthy
authors.forename: Anand
authors.initials: A
authors.lastname: Anbarasu
authors.forename: Sudha
authors.initials: S
authors.lastname: Ramaiah
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020134:Catalytic Domain; D047188:Chalcones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D055672:Static Electricity
chemical_list: D000962:Antimalarials; D047188:Chalcones; D015800:Protozoan Proteins; D011804:Quinolines; D007770:L-Lactate Dehydrogenase
keywords: CoMFA; anti-malarial compounds; molecular docking; quinolinyl chalcone derivatives