3-巯基-4-氧代戊基乙酸酯的合成和机理探讨

以α-乙酰基-γ-丁內酯为原料,经氯化、开环、脱羧、酯化和硫氢化钠的亲核取代合成3-巯基-4-氧代戊基乙酸酯,含量97%,总收率为75%。对它的合成机理进行了初步探讨。     

Enhanced Skin Permeation of Anti-Aging Peptides Using Bioactive Ionic Liquids at Low Concentrations

Delaying aging is an eternal goal for humanity. Acetyl hexapeptide-8 (AHP-8) is an effective skin anti-aging drug that locally interrupts the signal transmission of muscle contractions and promotes collagen production, thus smoothening wrinkles. However, its high molecular weight and strong hydrophilicity limit its skin permeation capacity. To solve this problem, an ionic liquid with excellent bioactivity, MAC, is synthesized from l -malic acid and l -carnitine and used as a permeation enhancer to improve the anti-aging effects of AHP-8. The ratio of MAC's components is optimized based on density functional theory calculations and cytotoxicity experiments. Low concentrations of MAC significantly increase AHP-8 transdermal delivery, reaching a maximum at 5-10 wt% MAC. The pro-permeation mechanism of MAC is investigated using molecular dynamics simulations, and the penetration enhancement and anti-aging performance of AHP-8 are demonstrated by conducting cellular, animal, and clinical experiments. The results show that MAC/AHP-8 outperforms AHP-8 in terms of collagen and hyaluronic acid synthesis, anti-inflammation, anti-oxidation, and inhibition of muscle contraction, thus significantly reducing the number and area of wrinkles and increasing skin moisture and elasticity. This study presents MAC as a simple and efficient transdermal vehicle for the clinical application of AHP-8.     

Anthracene-Walled Acyclic CB[n] Receptors: in vitro and in vivo Binding Properties toward Drugs of Abuse

We report studies of the interaction of six acyclic CB[n]-type receptors toward a panel of drugs of abuse by a combination of isothermal titration calorimetry and ¹H NMR spectroscopy. Anthracene walled acyclic CB[n] host ( M3 ) displays highest binding affinity toward methamphetamine (K_d=15 nM) and fentanyl (K_d=4 nM). Host M3 is well tolerated by Hep G2 and HEK 293 cells up to 100 μM according to MTS metabolic and adenylate kinase release assays. An in vivo maximum tolerated dose study with Swiss Webster mice showed no adverse effects at the highest dose studied (44.7 mg kg⁻¹). Host M3 is not mutagenic based on the Ames fluctuation test and does not inhibit the hERG ion channel. In vivo efficacy studies showed that pretreatment of mice with M3 significantly reduces the hyperlocomotion after treatment with methamphetamine, but M3 does not function similarly when administered 30 seconds after methamphetamine.