Design, Synthesis and SARs of 7-Deaza-4'-thioadenosine Derivatives as Multi-Kinase Inhibitors targeting Cancer Using Polypharmacology Approach

Abstract

Despite enormous research on cancer disease, the resistance crises due to which the single-target cancer therapy usually fails in clinics has not yet been overcome. To address the issue, simultaneously targeting more than one target those are involved in cancer growth and survival using the concept called polypharmacology has been currently a focus of attention among medicinal chemists. It has been well known that a key mechanism associated with the growth of cancerous cells is dysregulation of protein kinases activity. In this study, we designed and synthesized 7-deaza-4'-thioadenosine derivatives with the aim of identifying potent multi-kinase inhibitors possessing anticancer activity. We analyzed the structure-activity relationships of the hit compound to reveal the key pharmacophore required for obtaining the selectivity among several human protein kinases with reduced toxicity. The current research is expected to contribute much to the scientific community in the field of cancer.

Keyword: Polyphamacology, 7-deaza-4'-thioadenosine derivatives, multi-kinase inhibitors, anticancer