Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.
The relationship between exercise and cognition is an important topic of research that only recently began to unravel. Here, we set out to investigate the relation between motor skills, cognitive function, and school performance in 45 students from 8 to 14 years of age. We used a cross-sectional design to evaluate motor coordination (Touch Test Disc), agility (Shuttle Run Speed—running back and forth), school performance (Academic Achievement Test), the Stroop test, and six sub-tests of the Wechsler Intelligence Scale for Children-IV (WISC-IV). We found, that the Touch Test Disc was the best predictor of school performance (R2 = 0.20). Significant correlations were also observed between motor coordination and several indices of cognitive function, such as the total score of the Academic Achievement Test (AAT; Spearman's rho = 0.536; p ≤ 0.001), as well as two WISC-IV sub-tests: block design (R = −0.438; p = 0.003) and cancelation (rho = −0.471; p = 0.001). All the other cognitive variables pointed in the same direction, and even correlated with agility, but did not reach statistical significance. Altogether, the data indicate that visual motor coordination and visual selective attention, but not agility, may influence academic achievement and cognitive function. The results highlight the importance of investigating the correlation between physical skills and different aspects of cognition.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 1-5 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 1-5 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with inhibition rates of 18.0%-61.1% and 65.9%-87.3%, respectively. Compounds 1 and 5 were the most active compounds, inhibiting adenosine-diphosphate-induced platelet aggregation by 57.2% and 61.1%, respectively. The inhibitory rates for arachidonic-acid-induced platelet aggregation were similar for compound 2 (80.8%) and acetylsalicylic acid (ASA, 80%). After their oral administration to mice, compounds 1, 3, and 5 showed shorter mean bleeding times than ASA. Compounds 1 and 5 also protected against thromboembolic events, with survival rates of 40% and 33%, respectively, compared with 30% for ASA. In conclusion, these results indicate that these novel NSAIDs containing an NAH subunit may offer better antiplatelet and antithrombotic activities than ASA.
A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.
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