Hydroxamic Acid Hybrids for Lung Cancer Therapy

ABSTRACT Lung cancer is one of the most common and deadly cancers across the world nowadays, and the morbidity and mortality of lung cancer will continue to increase for a long period. Chemotherapy, which can kill cancer cells, shrink tumors, and improve patient survival and quality of life, plays a crucial role in lung cancer therapy. However, chemotherapy has several disadvantages, mainly manifested in severe side effects, limited efficacy, and the tendency to develop drug resistance. Histone deacetylase (HDAC) inhibitors, which work by inhibiting the activity of HDACs, can help to re‐express tumor‐suppressor genes that have been silenced due to epigenetic changes, thus inhibiting the growth and proliferation of lung cancer cells. Hydroxamic acid hybrids as potent HDAC inhibitors exhibited robust in vitro and in vivo efficacy against drug‐sensitive and drug‐resistant lung cancers, representing crucial templates in creating innovative anti‐lung cancer agents. This article will introduce the latest research progress on hydroxamic acid hybrids with anti‐lung cancer activity developed since 2020. The structure–activity relationships will be summarized, and the mechanisms of action will be discussed to provide references for future research.