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

Journal Article

2025

Published in: https://doi.org/10.1021/acsmedchemlett.5c00014

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.

• Publisher Name: ACS
• Volume Number: 16
• Issue Number: 5
• Pages: 819-828