NaClO-Mediated Cross Installation of Indoles and Azoles Benefits Anticancer Hit Discovery

Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. As a result, it is of significance to develop novel simple and effective synthetic installation of medicinal modules to promote drug discovery. Herein, we have developed a NaClO-mediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. This effective toolbox provides a convenient synthetic route to access a library of N-linked 2-(azol-1-yl) indole derivatives, and can be used for late-stage modification of drugs, natural products and peptides. Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI-H1975 cells, which give us a hit for anticancer drug discovery.

Automated summary

Innovations in synthetic chemistry play a crucial role in drug discovery and development. Developing simple and effective methods for synthesizing medicinal modules is of great significance. In this study, we successfully developed a NaClO-mediated cross installation of indoles and azoles, which are commonly found in drugs and natural products. This method provides a convenient route for accessing a library of N-linked 2-(azol-1-yl) indole derivatives and allows late-stage modification of drugs, natural products, and peptides. Furthermore, the biological screening of the library demonstrated promising anticancer activities against A549 and NCI-H1975 cells, providing a potential lead for anticancer drug discovery.