Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we investigated the anticancer properties of antiepileptic drugs and interlinked cancer and epileptic pathways. Our focus was primarily on those drugs that have entered clinical trials with positive results and those that provided good results in preclinical studies. Many contributing factors make cancer therapy fail, like drug resistance, tumor heterogeneity, and cost; exploring all alternatives for efficient treatment is important. It is crucial to find new drug targets to find out new antitumor molecules from the already clinically validated and approved drugs utilizing drug repurposing methods. The advancements in genomics, proteomics, and other computational approaches speed up drug repurposing. This review summarizes the potential of antiepileptic drugs in different cancers and tumor progression in the brain. Valproic acid, oxcarbazepine, lacosamide, lamotrigine, and levetiracetam are the drugs that showed potential beneficial outcomes against different cancers. Antiepileptic drugs might be a good option for adjuvant cancer therapy, but there is a need to investigate further their efficacy in cancer therapy clinical trials.
FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.