Identification of Trovafloxacin, Ozanimod, and Ozenoxacin as Potent c‐Myc G‐Quadruplex Stabilizers to Suppress c‐Myc Transcription and Myeloma Growth

c-Myc is a major oncogene that is estimated to result in almost all human cancers and the c-Myc downregulation has become an attractive strategy for cancer treatment. For it is hard to design compounds that can directly interact with the c-Myc protein, the DNA G-quadruplex (G4) was discovered in its promoter region which was referred to as a potential drug target for controlling c-Myc expression. In this study, a combined strategy of molecular docking-based virtual screening, molecular dynamics (MD) simulation, and molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculation was conducted on the existing FDA-Approved Drugs Library, eight compounds were selected for further experimental assay. Among them, five compounds exhibited dose-dependently anticancer activities against RPMI-8226 cells with IC50 values less than 18.4 μM. Further experiments showed that Trovafloxacin, Ozanimod, and Ozenoxacin decreased c-Myc mRNA level obviously and downregulated c-Myc expression significantly. In summary, compounds Trovafloxacin, Ozanimod, and Ozenoxacin might be regarded as new c-Myc G4 stabilizers for the treatment of c-Myc related cancers in the future.