Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid's Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations.

Lung cancer is a pervasive and challenging disease with limited treatment options, with global health challenges often present with complex molecular profiles necessitating the exploration of innovative therapeutic strategies. Single-target drugs have shown limited success due to the heterogeneity of this disease. Multitargeted drug designing is imperative to combat this complexity by simultaneously targeting multiple target proteins and pathways, which can enhance treatment efficacy and overcome resistance by addressing the dynamic nature of the disease and stopping tumour growth and spread. In this study, we performed the molecular docking studies of Drug Bank compounds with a multitargeted approach against crucial proteins of lung cancer such as heat shock protein 5 (BIP/GRP78) ATPase, myosin 9B RhoGAP, EYA2 phosphatase inhibitor, RSK4 N-terminal kinase, and collapsin response mediator protein-1 (CRMP-1) using HTVS, SP with XP algorithms, and poses were filtered using MM\GBSA which identified [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BenCarMethIn YlPro-Phosphonic Acid) (DB02504) as multitargeted drug candidate with docking and MM\GBSA score ranges from -5.83 to -10.66 and -7.56 to -50.14 Kcal/mol, respectively. Further, the pharmacokinetic and QM-based DFT studies have shown complete acceptance results, and interaction fingerprinting reveals that ILE, GLY, VAL, TYR, LEU, and GLN were among the most interacting residues. The 100 ns MD simulation in the SPC water model with NPT ensemble showed stable performance with deviation and fluctuations <2 Å with huge interactions, making it a promising multitargeted drug candidate; however, experimental studies are needed before use.

Effect of hematocrit, galactose and ascorbic acid on the blood glucose readings of three point-of-care glucometers.

Glucometers are commonly used in a variety of healthcare settings and use in critically ill patients should not be assumed without appropriate tool validation. The study objective was to evaluate the accuracy of three point-of-care glucometers (POCGs) to assess glucose concentration in human blood sample. The POCGs tested included three different instruments and utilized three factors (hematocrit [Hct], galactose and ascorbic acid) in glucose measurements to determine the glucometers' accuracy and compared to the reference laboratory biochemical analyzer (Cobs 8000, Roche, Basal, Switzerland). In this study, the Nova StatStrip glucometer showed no significant variation compared to the laboratory method at high glucose level with various Hct%. ACCU-Chek Inform II overestimated the glucose results at Hct 22% and underestimated at Hct 62%. The Freestyle glucometer showed lower glucose levels compared to the Cobas 8000 at Hct 62%. The ACCU-Check showed significant increase of blood glucose with low Hct% levels when compared to the laboratory method. The Freestyle showed a decreased level of glucose with high Hct 62% interference compared to the Cobas 8000. Galactose interference 100 and 200 mg/dL dramatically affected the accuracy of ACCU-Chek Inform II. Nevertheless, among all three POCGs in this study, the Nova StatStrip showed the most reliable and stable results for glucose level in the presence of interference. Especially, those in critical care units, whereas the Freestyle Precision Pro and ACCU-Chek Inform II were insufficiently accurate for critically ill patients.