Antiproliferative Activity of New Bis-Thionaphthoquinones in Cervical Cancer

Over the past decades, natural products have been a primary source of anticancer agents. Naphthoquinones, a large class of secondary metabolites, exhibit known anticancer activity. Thionaphthoquinones, which are naphthoquinones with added thiol groups, have demonstrated similar potential to their precursors. Cervical cancer is the third most common and fourth most lethal type of cancer among women worldwide. This study aimed to investigate the antiproliferative activity of new bis-thionaphthoquinones in cervical cancer cells. Five new molecules (D1-D5) were synthesized via multicomponent reaction and characterized by mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate antiproliferative activity in HeLa and NIH3T3 cells. Flow cytometry was employed to analyze deoxyribonucleic acid (DNA) fragmentation. PharmMapper was utilized for target fishing. Among the tested molecules, bis-thionaphthoquinone D4 exhibited the highest potency and selectivity, with a half maximal inhibitory concentration (IC50) of 42.7 μM and a selectivity index of 2.05. Additionally, it also induced DNA fragmentation, suggesting its potential to induce cell death. Carbonic anhydrase II was identified as the most likely target for D4. Therefore, bis-thionaphthoquinone D4 demonstrated both potency and selectivity, making it a promising drug candidate for the treatment of cervical cancer.