Purine scaffold Hsp90 inhibitors as mitochondria targeting anticancer and theranostics agents

Abstract

Mitochondria, the powerhouse of cell are a potential target in cancer treatment. Heat shock proteins (Hsp) and their paralogs have major role in coordinating the various functions including cell proliferation, metabolism and even apoptosis. The mitochondrial pool of Hsp90 and its mitochondrial paralog, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. On the other hand, theranostics refers to an appealing new approach to drug development wherein therapeutic modalities are combined with those associated with diagnostic imaging. The field has emerged as an interdisciplinary research area involving chemistry, material science, biology, and medicine that combine diagnostics and therapeutics, enabling early detection, targeted drug delivery and release, and monitoring of therapeutic response with the aid of imaging modalities in a single procedure. In this context, purine-scaffold Hsp90 inhibitor series has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. In this work we describe the design and synthesis of a few purine based molecules for mitochondrial TRAP1 targeting and theranostics application.