Organotin(IV) Dithiocarbamate Compounds Targeting A549 Lung Cancer Cells via Mitochondria-Mediated Apoptosis

ABSTRACT Lung cancer remains the leading cause of cancer-related deaths worldwide, with cisplatin as the primary chemotherapy despite its limitations. Organotin(IV) dithiocarbamates have emerged as promising anticancer agents due to their potent cytotoxicity and stability. This study reports the successful synthesis of four novel organotin(IV) dithiocarbamates: dimethyltin(IV) N -methyl- N -benzyldithiocarbamate (DioSn- 1 ), diphenyltin(IV) N -methyl- N -benzyldithiocarbamate (DioSn- 2 ), triphenyltin(IV) N -methyl- N -benzyldithiocarbamate (TriSn- 3 ), and triphenyltin(IV) N -ethyl- N -benzyldithiocarbamate (TriSn- 4 ). Their cytotoxicity against A549 lung carcinoma cells was evaluated via MTT assay, while Annexin V-FITC/PI staining determined the mode of cell death. DioSn- 2 , TriSn- 3 , and TriSn- 4 exhibited potent cytotoxicity (IC₅₀: 0.52–1.86 μM), whereas DioSn- 1 was inactive (IC₅₀ > 50 μM). Apoptotic features such as cell shrinkage and membrane blebbing were observed, with apoptosis rates ranging from 58% to 91%. DioSn- 2 was the most selective (SI = 6.45) and induced early DNA damage within 30 minutes, followed by mitochondrial depolarization and excessive ROS generation. Caspase-9 activation exceeded caspase-8, confirming intrinsic apoptosis. NAC treatment reduced apoptosis by 52%, highlighting oxidative stress as a key cytotoxic mechanism. These findings suggest DioSn- 2 as a promising alternative to cisplatin for lung cancer therapy.