Original Articles: 2011 Vol: 3 Issue: 2
Pyrimidinedione: Pharmacophore Optimization of Selective Thymidine Monophosphate Kinase inhibitors using Group QSAR Studies as Potential Antitubercular agents
Abstract
Tuberculosis (TB) is the second major cause of death from a single infectious agent among
adults in developing countries, followed by HIV. The emergence of multi-drug resistant strains of
Mycobacterium tuberculosis and revival of TB in the industrialized world due to HIV infections
has rendered the quest for new drugs against TB a priority. In this work an effort is made to
optimize the pharmacophore required for potent and selective inhibition of one essential enzyme
of nucleotide metabolism, viz., thymidine monophosphate kinase (TMPKmt), by selecting
reported series of TMPKmt inhibitors. A new Group-Based QSAR (G-QSAR) method which uses
descriptors evaluated for the fragments of the molecules, generated using specific fragmentation
rules for the selected dataset was carried out . G-QSAR was specifically done for knowing the
structure activity relationship for carrying out variations in substitution at specific substitution
sites. Also mathematical model for the prediction of activities of the new molecules was
developed. G-QSAR studies were carried out using VLife Molecular Design Suite (V Life MDS)
software.