Exploring The Impact of Two Novel DNA Minor Groove Binders on HCT-116 Cells: A Comprehensive Multi-Omics Analysis Using Mass Spectrometry

Colorectal cancer (CRC) poses a significant global health challenge, necessitating innovative therapeutic approaches. Despite advancements, current treatments encounter obstacles such as chemotherapy resistance and adverse effects due to non-selective targeting. DNA Minor Groove Binders (MGBs) present promising alternatives, targeting DNA structure without causing permanent damage. In this study, two novel MGB compounds were synthesized, MGB30 and MGB32, resembling distamycin, a natural DNA-binding agent. These compounds bind reversibly to the DNA minor groove, influencing DNA structure and inhibiting cancer growth-related enzymes. We conducted mutli-omics approach including metabolomics and proteomics on HCT-116 treated cells to explore the molecular mechanisms of action of MGB30 and MGB32 novel compounds using TIMS-QTOF-UHPLC-MS. We utilized four biological replicates for each treatment condition. By conducting a two-tailed independent student's t-test with q-value < 0.05, 12 metabolites and 187 dysregulated proteins were obtained after MGB30 treatment. Wile 41 metabolites and 409 dysregulated proteins were obtained after MGB32 treatment.