Glioblastoma (GBM) is a highly malignant
brain tumor characterized
by a heterogeneous population of genetically unstable and highly infiltrative
cells that are resistant to chemotherapy. Although substantial efforts
have been invested in the field of anti-GBM drug discovery in the
past decade, success has primarily been confined to the preclinical
level, and clinical studies have often been hampered due to efficacy-,
selectivity-, or physicochemical property-related issues. Thus, expansion
of the list of molecular targets coupled with a pragmatic design of
new small-molecule inhibitors with central nervous system (CNS)-penetrating
ability is required to steer the wheels of anti-GBM drug discovery
endeavors. This Perspective presents various aspects of drug discovery
(challenges in GBM drug discovery and delivery, therapeutic targets,
and agents under clinical investigation). The comprehensively covered
sections include the recent medicinal chemistry campaigns embarked
upon to validate the potential of numerous enzymes/proteins/receptors
as therapeutic targets in GBM.
The recurrence and associated side effects of modern treatment methods for urolithiasis highlight the need for a safer phytotherapy-based alternative medicine. In the present study, the seeds of Macrotyloma uniflorum (MUE) and leaves of Bryophyllum pinnatum (BPE) were evaluated for their antioxidant, antiurolithiatic, and wound healing potential. Phytochemical screening of extracts was carried out through gas chromatography-mass spectrometry analysis. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6sulfonic acid) diammonium salt (ABTS) assays were used to determine antioxidant potential of plant extracts. Percentage radical activity increased from 1.91% to 53.99% in DPPH assay and 39.26%-97.44% in ABTS assay, with an increase in concentration of BPE. Different concentrations of MUE also resulted in dosedependent antioxidant activity from 5.70% to 45.14% in DPPH assay and 17.96%-96.04% in ABTS assay. Extracts were investigated for their effect on calcium oxalate monohydrate (COM) crystals-induced Vero cell injury. BPE resulted in the retention of 98.5% viability after COM crystal exposure to Vero cells against the injured group (57.44%). Similarly, retained cell viability was found to be in the range of 77.4%-90.74% with different MUE concentrations. Wound healing potential was examined through scratch assay. Along with the prevention of cell injury, extracts also accelerated the wound closure rate as compared to control. Treatment with EC50 and EC90 of BPE resulted in 84.48% and 74.08% wound closure, respectively, as compared to the control group (73.79%). However, EC50 and EC90 of MUE resulted in 85.66% and 91.09% wound closure, respectively. The present study concludes the effectiveness of these herbal extracts in minimizing risk factors leading to urolithiasis.The interaction of calcium oxalate monohydrate (COM) crystals with renal tubular cells elevate the production of reactive oxygen species (ROS) and stimulate epithelial cell injury, leading to inflammation and eventually cell death [5,6]. Renal epithelial cells
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