World Journal of
Pharmaceutical and Life Sciences

DRUG DESIGN AND IN SILICO BINDING ANALYSIS OF PYRIMIDINE APPENDED THIAZOLIDINEDIONE ANALOGUES AS PPAR-???? AGONISTS

*Arunlal V. B. and G. Babu

ABSTRACT

Drug design is the creative process of finding new remedies based on the knowledge of a biological target. This work gave the various approaches of drug design, lead discovery, lead modification & various types of drug discovery. Drug design may have a significant role in the alteration of pharmakinetics of a lead molecule. The process of drug discovery by laboratory experiments is time consuming and very expensive as compared to computational methods. Thiazolidin-2,4-diones (TZDs) are primarily used as antidiabetic agents but also exhibit diverse therapeutic activities, such as antimicrobial, antiviral, anticancer, and antioxidant activities etc. The TZD nucleus plays a central role in the biological functioning of several essential molecules and possesses significant medicinal potential. The discovery of new TZD analogues is not easily attainable. Thiazolidinedione nucleus upon the substitution of various functional groups is provides a wide spectrum of biological activity by the use of different mechanism on different target sites. The present work attempted to explore the anticancer potential of TZDs on PPAR-? (peroxisome proliferator-activated receptor gamma) in breast cancer. Thiazolidinediones are synthetic PPAR-? agonists hence incorporation with pyrimidine derivatives expected the synergetic activity. Thiazolidinedione moiety has more specific binding interactions with the receptor sites but N-substituted Thiazolidine-2,4-dione derivatives (pyrimidine appended analogous) have been shown moderate interactions with receptors when compared with standard anticancer drug methotrexate. The results avail to understand the type of interactions that occur between pyrimidine linked thiazolidinediones analogues with PPAR-? binding site region and explain the importance of various computational tools in the designing of newer molecule against breast cancer.

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