The ongoing emergence of SARS-CoV-2 mutations underscores the urgent need for new antivirals that target key viral proteins. This study describes the design, synthesis, and evaluation of two series of 1,3,4-oxadiazole-tethered N-substituted isatin hybrids as inhibitors of the SARS-CoV-2 main protease (Mpro): 1,2,3-triazole-linked derivatives (9a–h) and pyrazole-linked derivatives (15a–d). Compounds 15a–c were identified as the most active derivatives in initial FRET-based screening. With an IC50 of 15.38 µM, 15c was the most effective inhibitor, as determined by subsequent enzymatic assays. 15a and 15b had IC50 values of 24.43 and 30.55 µM, respectively. The active chemicals inhibit Mprovia a noncompetitive/mixed mechanism (α = 0.41–0.44), at a KI value of 13.24 µM, according to enzyme kinetic studies. Additionally, the compounds exhibited favorable physicochemical and ADMET profiles and minimal cytotoxicity against normal IMR-90 cells. The stable predicted binding of the most active compound, 15c, within the Mpro active site was further supported by molecular docking and molecular dynamics simulations. Collectively, these findings identify 15c as the most active derivative in the present series and provide preliminary SAR insights that may guide further optimization of this scaffold as a potential class of SARS-CoV-2 Mpro inhibitors.
T. Al-Warhi, Md Sofequl Islam Mukim, Zainab M. Elsayed et al.· RSC Advances· 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
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
