Unlocking the power of imidazoquinolines: recent advances in anticancer and immunotherapeutic strategies

The challenges in drug discovery aiming to mitigate cancer progression are the thrust area of scientific research for several decades. Since the advent of heterocyclic chemistry, drug discovery programs have made significant achievements that lead to the development of numerous drugs with broad spectrum of potencies, contributing to both diagnostic and therapeutic advancements. Till date, efforts to discover more potent and efficient drug candidates are underway to minimize adverse side effects of existing chemotherapeutics. In view of the above, small-molecule agonists that can interact with different immune modulators like toll like receptor-7 (TLR-7) and TLR-8 are being investigated and explored. These candidates are expected to display profound effect on anti-tumoral activity by enhancing the production of proinflammatory cytokines. Recently, numerous imidazoquinoline derivatives with proven TLR agonist activities have emerged as promising anticancer therapeutics. With advancements in technology and the evolution of new scopes in drug discovery, different strategies are being adopted, particularly with the help of nanotechnology, immune-technology, combination drug chemistry, etc., to curb the progression of various types of cancers. Herein, the novel strategies for cancer therapeutics with imidazoquinolines reported in the last 5 years, their structure-activity relationship along with important synthetic schemes for important TLR agonists, are discussed.