Ultrasonication and RSM-based optimization of antioxidant activity, saccharide composition and fatty acids from Phoenix dactylifera L. Medjool date seeds influenced by ethanol

In response with the demand in date industry finding on sustainable solution for date seeds management and its bioactive rich constituent, current study envisaged the optimum condition for the ultrasound extraction of Phoenix dactylifera L. Medjool date seeds and its antioxidative activity by employing a three-level three-factor Box–Behnken design via response surface methodology (RSM). Ethanol (EtOH) concentration (50-80%), time (30-90 min) and temperature (40-70 °C) were the independent variables investigated for ABTS•+ scavenging antioxidant activity and subjected to analysis of variance (ANOVA). The optimum conditions for maximum antioxidant activity (60.93% ± 0.021) were achieved at 80% EtOH, 44 min and at 57 °C, where the effect of EtOH concentration were notably significant. The observed agreement between the experimental (60.93% ± 0.021) and predicted (60.35%) values indicated the employed model suitability while substantiates the successful implementation of RSM for optimizing extraction parameters. The optimized extract characterized through UPLC-QTOF/MS and GC-MS/MS, detailed the presence of saccharides (isomaltose, mannotriose and stachyose) and volatile compounds, namely 5 saturated fatty acids that encompassed within the 8.42% (w/w) of total fat obtained. This verifies the ability of the solvent mixture extracting fatty acids and saccharides even under high EtOH concentration

Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA)

Aurora-A kinase plays a central role in mitosis, where aberrant activation contributes to cancer by promoting cell cycle progression, genomic instability, epithelial-mesenchymal transition, and cancer stemness. Aurora-A kinase inhibitors have shown encouraging results in clinical trials but have not gained Food and Drug Administration (FDA) approval. An innovative computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA) was applied—aiming to identify novel Aurora-A kinase inhibitors—using seventy-nine reported Aurora-A kinase inhibitors to specify the best possible docking settings needed to fit into the active-site binding pocket of Aurora-A kinase crystal structure, in a process that only potent ligands contact critical binding-site spots, distinct from those occupied by less-active ligands. Optimal dbCICA models were transformed into two corresponding pharmacophores. The optimal one, in capturing active hits and discarding inactive ones, validated by receiver operating characteristic analysis, was used as a virtual in-silico search query for screening new molecules from the National Cancer Institute database. A fluorescence resonance energy transfer (FRET)-based assay was used to assess the activity of captured molecules and five promising Aurora-A kinase inhibitors were identified. The activity was next validated using a cell culture anti-proliferative assay (MTT) and revealed a most potent lead 85(NCI 14040) molecule after 72 h of incubation, scoring IC50 values of 3.5–11.0 μM against PANC1 (pancreas), PC-3 (prostate), T-47D and MDA-MB-231 (breast)cancer cells, and showing favorable safety profiles (27.5 μM IC50 on fibroblasts). Our results provide new clues for further development of Aurora-A kinase inhibitors as anticancer molecules