Том 25, № 19 (2025)

Glioblastoma (GB) remains a formidable challenge in oncology, with current treatment approaches providing only marginal improvements in patient outcomes. Despite significant advances in understanding its molecular and genetic characteristics, median survival for untreated patients remains distressingly low, emphasizing the urgent need for novel therapeutic strategies. This review comprehensively examines the standard first-line treatments for GB, including surgery, concomitant radio-chemotherapy, and maintenance chemotherapy, while highlighting the limitations of these approaches. Consequently, we explore emerging novel therapeutic modalities such as Oncolytic Viral Therapy with genetically modified oncolytic viruses that enhance the capabilities of antigen- presenting cells. These cells migrate to lymph nodes to recruit cytotoxic CD8+ T lymphocytes, directing them to the site of infection where they eradicate cells that promote tumour growth. Aptamer-based therapies, such as GMT-3, AS1411, GS24, GMT8, and Gint4.T, which exhibit specificity for their biological targets and can act as drug transporters by facilitating receptor-mediated transcytosis within the endothelial cells of the blood-brain barrier, thus improving drug delivery. Tumour-treating fields (TTFields) that have shown increased overall survival rates in patients. Personalized genomic medicine, driven by biomarkers, which provokes immune responses tailored to the tumour’s specific antigens, thereby customizing patient-specific treatments to improve effectiveness. By synthesizing current evidence and recent breakthroughs, we underscore the potential use of advancing novel therapies to address the unmet clinical needs of GB patients and ultimately enhance their overall survival and quality of life.

Aim:The present study aims to identify the synthesis and structural characterization of acyl hydrazone- sulfonamide-containing compounds that were tested in vitro on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII.

Methods:Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized via a three-step synthetic pathway starting from the commercially available 4-sulfamoyl benzoic acid. Structural characterizations of the final compounds were assessed through IR IR, 1H-NMR, 13C-NMR, and elemental analyses. The in vitro profiling activity of the final compounds on the Carbonic Anhydrases (CAs; EC 4.2.1.1) I, II, IX, and XII were performed by means of the stopped-flow technique and revealed nanomolar inhibitory potencies on the selected targets. Molecular docking and molecular dynamic simulations afforded a detailed understanding of the binding modes of the most effective compounds.

Results:We reported the synthesis and structural characterization of 25 acyl hydrazone-sulfonamide-containing compounds that were tested in vitro on the hCAs I, II, IX, and XII isoforms for their inhibitory features. Overall, all compounds showed nanomolar inhibition potencies on the panel of hCAs considered, and their binding modes were deciphered by means of in-silico studies. Molecular docking followed by MD simulations confirmed the stability of 4l-hCA I, 4n-hCA II, 4t-hCA II, 4v-hCA XII, and 4w-hCA XII complexes.

Conclusion:This study presents a deep understanding of the structural determinants influencing the affinity and selectivity of the designed compounds towards different hCAs, thus offering valuable insights for further optimization and development in the field.

Introduction:Cancer is a group of diseases caused by uncontrollable cell growth. Herbal medicines, derived from plants, have been used for centuries across cultures for their therapeutic benefits, effectively treating conditions like cancer. This study represents the anticancer effects of fractions of some medicinal plant extracts along with their apoptotic studies and their induction through p53-mediated Bax and Bcl-2 mRNA expression in HepG2 and U87MG cells.

Methods:The fractionation of crude methanolic extracts was done using Column Chromatography and Thin Layer Chromatography. The fractions were analysed for cytotoxicity against both the cell lines by MTT assay. Cancer cells were treated with 2 most active fractions and their mechanism of apoptosis induction was assessed by Flow Cytometry studies and the mRNA expression levels of p53, Bax, and Bcl-2 were determined by Reverse Transcriptase PCR. The presence of phytoconstituents in the active fractions was analysed by GC-MS.

Results:The active fractions revealed the apoptosis induction in both the cell lines and the RT-PCR studies suggested the mechanism of apoptosis induction through upregulation of p53 and Bax and downregulation of Bcl-2 mRNA. The GC-MS analysis of active fractions from Balanites aegyptiaca and Pterocarpus marsupium revealed the presence of phytochemicals such as 4-O-Methylmannose, Oleic acid, Erucic acid, etc. which might have contributed to the anti-proliferative and apoptotic effects of these fractions.

Discussion:4-O-Methylmannose was the major component identified with the highest peak area of 59%. The fractions from all the 4 plant extracts demonstrated significant cytotoxic effects on the liver (HepG2) and brain (U87MG) cancer cell lines, with particular emphasis on the active fractions BA FII, PM FII, and PM FIII. Additionally, the mechanisms of apoptosis induction through the modulation of p53, Bax, and Bcl-2 pathways, along with the presence of bioactive compounds further support the anticancer efficacy of these plant extracts. Also, to the best of our knowledge, this is the first study on fractions of Balanites aegyptiaca and Pterocarpus marsupium against U87MG cells.

Conclusion:The results highlight the promising potential of plant-derived natural products as anticancer agents. These findings provide valuable insight into the potential of herbal medicines and encourage further exploration of plant-based therapies for cancer treatment.