Morpholine-Substituted Tetrahydroquinoline Derivatives as Potential mTOR Inhibitors: Synthesis, Computational Insights, and Cellular Analysis

Abstract

Cancer is one of the leading causes of death worldwide, and scientists are constantly searching for better treatments. This study focuses on developing new drug-like molecules that can block a key protein called mTOR, which plays a crucial role in cancer cell growth and survival. In this manuscript, we designed and synthesized eight new tetrahydroquinoline analogs and evaluated their ability to stop the growth of lung and breast cancer cells while ensuring that they do not harm normal cells. The most promising compound, 10e, showed exceptional cytotoxicity for lung cancer cells at very low doses and worked even better than existing cancer drugs, like Everolimus and 5-fluorouracil. Advanced computer simulations helped confirm how these compounds attach to the mTOR protein and block its function. Further investigation revealed that these compounds trigger a natural process called apoptosis, which results in programmed cell death. These findings suggest that the novel THQ derivatives, especially 10e, could be strong candidates for future cancer treatments. With further testing, they may help create safer and more effective drugs for patients with lung and breast cancer.