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.
Shoaib Khan, Tayyiaba Iqbal, B. N. Murtaza et al.· Future Medicinal Chemistry· 0 citations
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.
Kazma Batool, T. Al-Warhi, A. Şenol et al.· RSC Advances· 0 citations
The epidermal growth factor receptor (EGFR) is a key regulator of malignant cell growth and survival, making it an attractive target for cancer therapy. In this study, a new series of thiazole derivatives was rationally designed and synthesized as potential EGFR inhibitors and evaluated for their antiproliferative activity against two human colon cancer cell lines (HCT-116 and HT29). Several compounds exhibited potent anticancer activity, with compound 4j showing the highest potency, displaying half-maximal inhibitory concentration (IC50) values of 2.10 and 1.91 µM against HCT-116 and HT29 cells, respectively. Owing to its superior antiproliferative activity, compound 4j was further evaluated for EGFR inhibitory activity and demonstrated remarkable potency with an IC50 value of 0.27 µM. In addition, 4j exhibited a favorable selectivity index toward normal WI38 cells and effectively induced apoptosis through modulation of Bax, Bcl-2, and p53 expression. Molecular docking demonstrated strong binding interactions of 4j within the EGFR active site, while its ADME predictions supported its favorable drug-like profile. Overall, compound 4j represents a promising lead candidate for the development of novel EGFR-targeted anticancer agents.
Amani M. R. Alsaedi, Alaa M. Abu Alnjaa, Amel S. Younes et al.· Future Medicinal Chemistry· 0 citations
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