AUTHOR=Ahmed Nafees , Anwar Sirajudheen , Thet Htar Thet 

TITLE=Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents

JOURNAL=Frontiers in Chemistry

VOLUME=5

YEAR=2017

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2017.00036

DOI=10.3389/fchem.2017.00036

ISSN=2296-2646

ABSTRACT=<p>The <italic>Plasmodium falciparum</italic> Lactate Dehydrogenase enzyme (<italic>Pf</italic>LDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The <italic>Pf</italic>LDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of <italic>Pf</italic>LDH, we have used Discovery studio to perform molecular docking in the active binding pocket of <italic>Pf</italic>LDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between <italic>in silico</italic> and <italic>in vitro</italic> results. Based on docking results, a highly predictive 3D-QSAR model was developed with <italic>q</italic><sup>2</sup> of 0.516. The model has predicted <italic>r</italic><sup>2</sup> of 0.91 showing that predicted IC<sub>50</sub> values are in good agreement with experimental IC<sub>50</sub> values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.</p>