Employing an intramolecular cycloaddition reaction, we have developed a series of SO prodrugs with tunable release rates with half-lives ranging from minutes to days.

A new xanthone glycoside, 1,3,5,6-tetrahydroxyxanthone-C-4-β-d-glucopyranoside was isolated from the methanol extract of Mangifera indica leaves (Anacardiaceae) growing in Egypt. The structure was clarified by 1D and 2D-NMR spectroscopic data. The physicochemical properties of the compound such as lipophilicity, solubility, and formulation considerations were predicted via in silico ADMET technique using the SwissADME server. This technique provided Lipinski’s rule of five, such as GIT absorption, distribution, metabolism, and skin permeation. The in vitro inhibitory activities against aging-mediated enzymes such as collagenase, elastase, hyaluronidase, and tyrosinase were assessed. The compound exhibited remarkable anti-collagenase, anti-elastase, anti-hyaluronidase, and anti-tyrosinase effects with IC50 values of 1.06, 419.10, 1.65, and 0.48 µg/mL, respectively, compared to the positive control. The compound showed promising predicted aqueous solubility and reasonable skin penetration suggesting the suitability of the compound for topical formulation as an anti-aging agent for cosmetic preparations.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a, 4b, and 5d showing 93-100% maximum inhibition of CHIKV replication in cell-based assay having EC90 of 8.76-9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a, 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β-unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug-likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization.

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