Design and Synthesis of π-Extended Resveratrol Analogues and In Vitro Antioxidant and Anti-Inflammatory Activity Evaluation.

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.

Effects of Cracking Test Conditions on Estimation Uncertainty for Weibull Parameters Considering Time-Dependent Censoring Interval.

It is extremely difficult to predict the initiation time of cracking due to a large time spread in most cracking experiments. Thus, probabilistic models, such as the Weibull distribution, are usually employed to model the initiation time of cracking. Therefore, the parameters of the Weibull distribution are estimated from data collected from a cracking test. However, although the development of a reliable cracking model under ideal experimental conditions (e.g., a large number of specimens and narrow censoring intervals) could be achieved in principle, it is not straightforward to quantitatively assess the effects of the ideal experimental conditions on model estimation uncertainty. The present study investigated the effects of key experimental conditions, including the time-dependent effect of the censoring interval length, on the estimation uncertainties of the Weibull parameters through Monte Carlo simulations. The simulation results provided quantified estimation uncertainties of Weibull parameters in various cracking test conditions. Hence, it is expected that the results of this study can offer some insight for experimenters developing a probabilistic crack initiation model by performing experiments.

Uncertainty Evaluation of Weibull Estimators through Monte Carlo Simulation: Applications for Crack Initiation Testing.

The typical experimental procedure for testing stress corrosion cracking initiation involves an interval-censored reliability test. Based on these test results, the parameters of a Weibull distribution, which is a widely accepted crack initiation model, can be estimated using maximum likelihood estimation or median rank regression. However, it is difficult to determine the appropriate number of test specimens and censoring intervals required to obtain sufficiently accurate Weibull estimators. In this study, we compare maximum likelihood estimation and median rank regression using a Monte Carlo simulation to examine the effects of the total number of specimens, test duration, censoring interval, and shape parameters of the true Weibull distribution on the estimator uncertainty. Finally, we provide the quantitative uncertainties of both Weibull estimators, compare them with the true Weibull parameters, and suggest proper experimental conditions for developing a probabilistic crack initiation model through crack initiation tests.