Hexonic derivatives as human GABA-AT inhibitors: A molecular docking approach

Human ?-aminobutyric acid aminotransferase (GABA-AT), a pyridoxal phosphate dependent enzyme is responsible for the degradation of the inhibitory neurotransmitter GABA. Currently, GABA-AT is a potential drug target for epilepsy due to the selective inhibition in brain. In this computational study, we mainly focus on screening of novel lead candidates against GABA-AT using hexonic derivatives. Structure based virtual screening is performed in Vina that screened top hits based on least binding affinity. Further re-docking on hits is performed in AutoDock results in identification of leads with favorable binding energy and hydrogen bond interactions confirmed the effective inhibition. In conclusion, leads 3-aminohex-5-enoic acid and AG-E-60842 can acts as specific leads for GABA-AT and assist in discovery of novel anti-epileptic drugs

Advancements in polysaccharide-based carriers for eco-friendly fungicide delivery

The demand for sustainable agricultural practices has led to an increased interest in using polysaccharide carriers for the delivery of fungicides. This review provides a comprehensive evaluation of chitosan, alginate, and cellulose as effective delivery systems, focusing on their respective loading capacities and controlled release profiles. Recent advancements in the synthesis and characterization of these biopolymers highlight their potential to improve fungicide efficacy while reducing environmental impact. Comparative analysis of existing studies reveals variability in encapsulation efficiency and release kinetics, which stem from the unique physicochemical properties of each polysaccharide. Additionally, we address ongoing debates regarding the best carrier choice, emphasizing the importance of understanding the interactions between carrier composition, environmental conditions, and fungicide performance. The objective of this review is to clarify the advantages and limitations of polysaccharide-based carriers, identify key factors affecting their effectiveness, and suggest future research directions aimed at developing eco-friendly fungicide formulations. Through this exploration, we aim to contribute valuable insights that will inform the design of sustainable pesticide delivery systems, aligning with the goals of contemporary agriculture and environmental safety

Combinatorial Delivery of Gallium (III) Nitrate and Curcumin Complex-Loaded Hollow Mesoporous Silica Nanoparticles for Breast Cancer Treatment

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body’s circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.</jats:p