Anticancer Activity and Molecular Docking Studies of Selected Benzoxazole Derivatives as Apoptosis Inducers in Non-Small Cell Lung Cancer

Abstract

Objective: Non-small cell lung cancer (NSCLC), the most prevalent type of lung cancer, remains the leading cause of cancer-related deaths worldwide. Late-stage diagnosis and resistance to conventional treatments highlight the need for further research into its molecular mechanisms. This study aimed to evaluate the anticancer effects of several benzoxazole derivatives (2-(4-tert-butylphenyl)-5-nitrobenzoxazole (1a), 2-(4-tert-butylphenyl)-6-nitrobenzoxazole (1b), 2-(2,3-dimethylphenyl)-5-nitrobenzoxazole (2a), and 2-(2,3-dimethylphenyl)-6-nitrobenzoxazole (2b)) on the viability of A549 cells. Materials and Methods: Cell viability was assessed using the MTT assay. We also performed a molecular docking study to investigate the interactions between the benzoxazole derivatives and caspase-3, a key executioner caspase involved in apoptosis. Results: The benzoxazole derivatives coded 1a, 1b, 2a, and 2b exhibited anticancer activity against A549 cells, with half-maximal inhibitory concentration (IC50) values of 17.41 +/- 0.16, 20.50 +/- 0.08, 32.17 +/- 0.08, and 31.13 +/- 0.07 & micro;M, respectively. Among the tested benzoxazoles, 1a and 1b showed activity comparable to cisplatin (IC50=19.65 +/- 0.09 & micro;M). According to the docking results, all compounds demonstrated satisfactory docking scores ranging from-4.339 to-5.202 kcal/mol. Conclusion: Our results demonstrate that the benzoxazole derivatives 1a and 1b exhibit significant anticancer effects by inhibiting lung cancer cell proliferation at low concentrations, similar to cisplatin. The structure-activity relationship suggests that substitution of a phenyl group at the 2-position of the benzoxazole ring with a tert-butyl group at the para position enhances anticancer activity against A549 cells. This preliminary study indicates that these benzoxazole derivatives have promising potential as cytotoxic agents for the treatment of