Synthesis and evaluation of C3 substituted chalcone-based derivatives of 7-azaindole as protein kinase inhibitors

Abstract

Chalcones are a group of naturally occurring or synthetic compounds which possess a wide range of biological activities. In this paper, a series of twenty-three 7-azaindole-chalcone hybrids (5a-w) were synthesized and evaluated as potential protein kinase inhibitors. Analyses of structure-activity relationships revealed that some of these compounds exhibit significant activity against Haspin kinase, with compounds 5f and 5q exhibiting IC₅₀ values of 0.47 and 0.41 µM, respectively. Furthermore, 5f also inhibits cyclin-dependent kinase 9 (CDK9/CyclinT) in a micromolar potency (IC₅₀ = 2.26 µM). This novel dual-target inhibitor is a promising lead for the development of chemopreventive/chemotherapeutic agents.

Keywords: 7-azaindole; CDK9/CyclinT; Haspin; chalcone; dual inhibitor; protein kinase; structure-activity relationships.