Design, Synthesis, Characterisation, and Evaluation of Substituted Quinolin-2-one Derivatives as Possible Anti-lung Cancer Agents.

Background: According to 2022, the estimated number of cancer cases in India was found to be 1,461,427. Lung cancers are the leading cause of death among Indian males. Research on cancer has been conducted to develop better treatments that are safe and effective and could be used to diagnose cancer at an early stage. It was found that quinolin-2-one possesses anticancer activity, which led us to synthesize substituted quinolin-2-one derivatives that can provide a longer future to cancer patients and decrease the risk of dying from cancer.

Objective: This study aimed to carry out the design, synthesis, characterisation, and evaluation of novel substituted quinolin-2-one analogues as possible anti-lung cancer agents.

Methods: Compound III a/III b on reaction with acids, sodium acetate and ethylchloroacetate, substituted benzaldehyde, phthalic anhydride, and 2N sodium hydroxide yielded compounds IV a/ IV b, V a/ V b, VI a/ VI b, VI c/ VI d, VI e/ VI f, VII a/ VII b, and VIII a/ VIII b, respectively.

Result: Among all the synthesised derivatives, compound VII a was found to be most potent with a MolDock score of -132.78 as compared to standard drug imatinib (-114.37) and active ligand 4- anilinoquinazoline (-126.71). All the synthesized derivatives showed a good ADME profile, but compound VII a showed the best ADME data among all the synthesised derivatives. All the synthesised compounds were tested for their in vitro anticancer activity against the Hop-62 (human lung cancer) cell line, out of which compound VII a was found to be most potent, with a percent control growth of -51.7% at a concentration of 80 μg/ml, which was in comparable to the positive control, Adriamycin (-70.5%) and standard imatinib (-84.0%).

Conclusion: Compound VII a showed the highest MolDock score and was most potent against human lung cancer cell line Hop-62.