BackgroundGlioblastomas arise from multistep tumorigenesis of the glial cells. Despite the current state‐of‐art treatment, tumor recurrence is inevitable. Among the innovations blooming up against glioblastoma, drug repurposing could provide profound premises for treatment enhancement. While considering this strategy, the efficacy of the repurposed drugs as monotherapies were not up to par; hence, the focus has now shifted to investigate the multidrug combinations.AimTo investigate the efficacy of a quadruple‐combinatorial treatment comprising temozolomide along with chloroquine, naringenin, and phloroglucinol in an orthotopic glioma‐induced xenograft model.MethodsAntiproliferative effect of the drugs was assessed by immunostaining. The expression profiles of WNT/β‐catenin and apoptotic markers were evaluated by qRT‐PCR, immunoblotting, and ELISA. Patterns of mitochondrial depolarization was determined by flow cytometry. TUNEL assay was performed to affirm apoptosis induction. In vivo drug detection study was carried out by ESI‐Q‐TOF MS analysis.ResultsThe quadruple‐drug treatment had significantly hampered glioma proliferation and had induced apoptosis by modulating the WNT/β‐catenin signaling. Interestingly, the induction of apoptosis was associated with mitochondrial depolarization. The quadruple‐drug cocktail had breached the blood–brain barrier and was detected in the brain tissue and plasma samples.ConclusionThe quadruple‐drug combination served as a promising adjuvant therapy to combat glioblastoma lethality in vivo and can be probed for translation from bench to bedside.

A series of [Mn(CO)3(L)Br] complexes (1–5) are synthesized using azachalcones as ligands, wherein they are coordinated to the manganese metal through the nitrogen and oxygen donor atoms. Their characterization using various spectroscopic techniques, stability analysis in dimethyl sulfoxide solvent, photodecomposition analysis, and antiproliferative effect are reported herein. These complexes release CO upon exposure to green light radiation. DFT and TD‐DFT investigations are also reported to gather information regarding the electronic features of these complexes.

Introduction Glioma, coined as a “butterfly” tumor associated with a dismal prognosis. Marine algal compounds with the richest sources of bioactive components, act as significant anti-tumor therapeutics. However, there is a paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. Therefore, the present study aimed to evaluate the synergistic anti-proliferative, anti-inflammatory and pro-apoptotic effects of Fucoidan with Temozolomide in in vitro and in silico experimental setup. Methodology The anti-proliferative effects of Temozolomide and Fucoidan was evaluated on C6 glioma cells by MTT and migration assay. Modulation of inflammatory markers and apoptosis induction was affirmed at the morphological and transcriptional level, by dual staining and gene expression. Molecular docking (MD) and molecular dynamics simulation (MDS) studies were performed against the targets to rationalize the inhibitory effect. Results The dual-drug combination significantly reduced the cell viability and migration of glioma cells in a synergistic dose-dependent manner. At the molecular level, the dual-drug combination significantly down-regulated inflammatory genes with a concomitant upregulation of pro-apoptotic marker. In consensus with our in vitro findings, molecular docking and simulation studies revealed that the anti-tumor ligands: Temozolomide, Fucoidan with 5-(3-Methy1-trizeno)-imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) had the potency to bind to the inflammatory proteins at their active sites, mediated by H-bonds and other non-covalent interactions. Conclusion The dual-drug cocktail of TMZ and FU may act as a potential therapeutic adjuvant for patients with glioma. However, rigorous pre-clinical experimental evidence is warranted for the possible translation of this combination from bench to bedside

Background: An important hallmark of glioblastoma aggressiveness is its altered metabolism of glucose. This metabolic shift wherein the tumor cells employ aerobic glycolysis regardless of oxygen availability via reprogramming of mitochondrial oxidative phosphorylation is known as the Warburg effect. Previous literatures have linked this metabolic reprograming to tumor progression glioblastoma cell proliferation making it a key target for targeted drug therapy. Objective: To evaluate the anti-Warburg efficacies of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in preclinical glioblastoma models. Methodology: Based on this lacuna, the current study aimed to explore the therapeutic efficacy of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in attenuating Warburg effect and glucose uptake in glioblastoma both in vitro and in vivo. Results: Our results showed that the triple-drug combination had significantly reduced glucose uptake and reversed the Warburg effect in glioblastoma cells and in the xenograft-induced glioma rat model. Conclusion: Thus, the triple-drug combination would serve as an effective therapeutic regime to hamper glioblastoma progression via altering glucose metabolism and improve the overall prognosis in patient setting.