A comprehensive review on bioactive fused heterocycles as purine-utilizing enzymes inhibitors

Abstract

Purine-utilizing enzymes (PUEs) are involved in the control of biological actions of nitrogen-containing bases, purines and pyrimidines, by participating in their catabolism, and this has made them a topic of considerate interest. The heterocyclics, as purine-utilizing enzyme inhibitors (PUEIs), play a vital role in a number of diseases, e.g., malaria, cancer, rheumatoid arthritis, inflammation, tissue rejection, and autoimmune disorders. The present review is first of its kind covering the literature up to 2014 on the advances in broad-spectrum medicinal activities exhibited by heterocycles as PUEIs. The drug designing of the purine and pyrimidine antimetabolites is based on the structural mimicking of the existing compounds. The basic consideration during the designing of this class is the introduction of small structural changes without the alteration of basic skeleton of pharmacophore. The balance between the existing empirical approach and rational approach is yet to be maintained during the design and synthesis of new PUEIs by combining in vivo, in vitro, and in silico methods. The data compiled in the present manuscript on SARs, IC50s, Kis, Km, in silico studies, and their reported X-ray co-crystal structures with PUEs will offer the researchers the rational approaches for the design and development of selective and specific PUEIs devoid of adverse effects.