Indoles-A Targeting the PI3K/Akt/mTOR Pathway: Recent Advances in Strategic Design, Mechanism, and Future...

Indole derivatives are known to be a diverse group of compounds that are potentially useful in the quest for new anticancer agents, especially because of their ability to regulate important cellular signaling pathways involved in cancer development. Of these, the PI3K/Akt/mTOR pathway is a dominant regulator of cell growth, proliferation, metabolism, and survival. Their dysregulation is seen in a broad range of cancers. The structural features of the indole scaffold make it possible to design potent derivatives. These are selective for the PI3K/Akt/mTOR pathway, with potential for greater specificity and lower toxicity than traditional treatments. This review critically assesses recent developments in the design, synthesis, and biological activity of indole-derived molecules as anticancer drugs, focusing on their modes of action, such as kinase inhibition and induction of apoptosis. Emphasizing natural and synthetic indole derivatives, the report covers their cytotoxic activity on different cancer cell lines and describes structure-activity relationships for further drug development. This review presents both traditional and novel synthetic approaches that demonstrate the chemical flexibility of the indole unit. Together, these results point out the advantages of indole derivatives as multitarget drugs for the treatment of cancer, in part through disruption of the PI3K/Akt/mTOR pathway, and suggest directions for future investigation as precision drugs in cancer therapy.