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Development of a less toxic dichloroacetate analogue by docking and descriptor analysis



Kannan Subramanian1, Anand S Ramaian2



1Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand. 2Department of Biotechnology, Sri Venkateswara College of Engineering, Pennalur, Sriperumbudur 602 105, India


E-mail*; * Corresponding author


Article Type






received  January31, 2010; revised May10, 2010; accepted  June8, 2010; published online July6, 2010




Dichloroacetate (DCA) is a synthetic compound that promotes the activity of pyruvate dehydrogenase (PDH) by inhibiting its repressor protein called pyruvate dehydrogenase kinase (PDHK). The activation of PDH leads to a reduction in ambient cellular lactate concentrations both in vitro and in vivo which contributes to the therapeutic use of DCA in the treatment of systemic lactic acidosis in humans. The therapeutic potential of DCA is now being explored in disorders that are accompanied by elevations of lactate concentration such as in hypoxic cancer cells. Yet conflicting evidence regarding its mutagenic potential has been a major setback in its clinical trials. Hence, docking and descriptor analysis of halogen substituted DCA analogues were performed to find out a drug candidate with less toxicity and better binding affinity than DCA. The Docking analysis was carried out using human PDHK isozyme 2, the physiological receptor for DCA. Bromo(iodo)acetate and Diiodoacetate were found out to be the plausible analogues of DCA from this study. 




PDH, PDHK, DCA, Docking and descriptor analysis.




Subramanian et al, Bioinformation 5(2): 73-76 (2010)


Edited by


P. Kangueane







  Biomedical Informatics



  This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.