Development of indole hybrids for potential lung cancer treatment-part I: nitrogen-containing six-membered aromatic heterocycles

Lung cancer is the most prevalent invasive malignancy and the leading cause of cancer-related death. Chemotherapy is vital for lung cancer therapy, but multidrug resistance is responsible for the majority of lung cancer fatalities, creating an imperative demand to develop novel chemotherapeutics. Indole is a valuable anti-lung cancer pharmacophore since its derivatives could act on lung cancer cells through various mechanisms. Notably, indole hybrids could inhibit multiple targets simultaneously and have the potential to overcome the shortcomings of traditional chemotherapeutics. Moreover, many indole hybrids such as the indole-pyrimidine hybrid osimertinib and the indole-hydroxamic acid hybrid panobinostat, are either under clinical evaluations or have already been approved for lung cancer therapy. This indicates that the rational design of indole hybrids represents a highly prospective approach for the development of new anti-lung cancer chemotherapeutic agents. This review focuses on exploring the anti-lung cancer therapeutic potential of indole hybrids and delves into their action mechanisms as well as structure-activity correlations, covering articles published between 2021 and present. The ultimate goal is to offer a foundation for the rational design of indole hybrids in the future.