S. M. Gomha

Design, synthesis, and computational assessment of bis‑oxadiazole ligands targeting α-amylase and α-glucosidase: DFT, docking, and ADME studies.

AIM Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, mainly due to postprandial glucose elevation. Inhibition of carbohydrate-hydrolyzing enzymes such as α-glucosidase and α-amylase is an effective strategy for its management. This study aimed to design, synthesize, characterize, and evaluate a series of bis-oxadiazole derivatives as potential anti-diabetic agents. METHODS The target compounds were synthesized via multistep organic synthesis and structurally confirmed using spectroscopic techniques including FTIR, NMR, and HRMS. The in-vitro anti-diabetic potential was assessed through α-glucosidase and α-amylase inhibition assays. In addition, molecular docking studies were performed to investigate binding interactions and conformational stability within the active sites of both enzymes. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling was also carried out to evaluate drug-likeness and pharmacokinetic properties. RESULTS Among the synthesized derivatives, compound 10 exhibited the most potent activity, showing IC50 values of 1.80 and 2.10 μM against α-amylase and α-glucosidase, respectively, in comparison with the positive control acarbose (IC50 = 5.50 and 5.60 μM, respectively). Compound 10 exhibited the most potent inhibitory activity against both enzymes, showing strong binding affinity and key hydrogen-bonding and hydrophobic interactions in docking studies. The spectroscopic characterization confirmed the successful formation of all target compounds. ADMET analysis indicated favorable pharmacokinetic and toxicity profiles for the most active derivatives. CONCLUSION The combined experimental and computational results demonstrate significant structure-activity relationships within the bis-oxadiazole scaffold, identifying compound 10 as a promising lead candidate for further optimization as a dual enzyme inhibitor for diabetes management.

Design, synthesis and DFT analysis of a highly selective chromenylium based fluorescent probe for cellular imaging and selective detection of sulfite ions

Sulfite (SO32−) is a significant analyte that is frequently employed as a food and beverage sector preservative but its excessive consumption might lead to negative health effects. Therefore, it is important to develop ultra-sensitive and ultra-selective sulfite detection methods. Herein, we demonstrate the design, synthesis and application of a highly selective fluorescent probe for fast and sensitive detection of sulfite ions. The interaction between this probe and SO32− ions induced a fluorescence signal (quenching) which made it possible to monitor the ions in a highly selective manner amongst various competing anions. Furthermore, the probe exhibited an excellent detection capability within a wide linear range and a high sensitivity with low detection limit (1.44 µM). Besides, the probe was applied for the analysis of sulfite ions in real samples as well as for cell imaging. Further validation of the suggested sensing mechanism was obtained from density functional theory (DFT) calculations, which showed substantial variation in the energy gaps between HOMO–LUMO, charge distribution, and intramolecular charge transfer (ICT). DFT calculations confirmed that the nucleophilic attack of SO32− on the π-conjugated system of the probe causes inhibition of ICT and fluorescence quenching behavior. The above findings clearly highlight the efficiency of the designed probe as an analytical tool for detecting sulfite ions in the environment and food safety applications.

Green Synthesis, Molecular Modelling, and ADME Evaluation of Functionalized Pyridine Derivatives as Potential SARS-CoV-2 Inhibitors