Synthesis of Marine-Inspired Multifaceted DNA Damaging Spirooxindoles Combating NSCLC and Associated Bacterial Infection

Targeted therapeutics have gained prominence in combating non-small cell lung carcinoma (NSCLC) and opportunistic bacterial infections like Staphylococcus aureus (S. aureus). This study explores dual-acting marine-inspired spirooxindoles to limit NSCLC and opportunistic bacteria. Pharmacophoric motifs from antitumor and antibacterial marine products were merged into a new series of pyrazole-clubbed spirooxindoles via a stereoselective [3 + 2] cycloaddition reaction. MTT screening identified 4e, 4i, and 4p-4s as potent cytotoxic agents, with 4p showing exceptional activity (IC50 = 0.042 μM) and tumor selectivity (SI = 58.28). 4p exhibited antibacterial efficacy against S. aureus (MIC = 25 μg/mL). DNA damage studies using a terbium(III) chloride biosensor revealed 4p's ability to damage both calf thymus and S. aureus DNA at low concentrations. Docking simulations presumed that 4p binds between DNA strands, while apoptosis studies indicated it induced G1/S phase cell cycle arrest and increased A549 apoptosis by 33.65%. These findings highlight 4p as a promising lead for further studies.