Synthesis and Biological Evaluation of Halogenated E-Stilbenols as Promising Antiaging Agents

Abstract

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations of reactive oxygen species. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RSV) plays a critical role in slowing the aging process but has a poor bioavailabity after oral intake. In this present work, a series of RSV derivatives was designed, synthesized, and evaluated as potential antioxidant agents. These derivatives contain substituents with different electronic and steric properties in different positions of aromatic rings. This kind of substituents affects the activity and the bioavailability of these compounds compared with RSV used as reference compound. Studies of Log P values demonstrated that the introduction of halogens gives the optimum lipophilicity to be considered promising active agents. Among them, compound 6 showed the higher antioxidant activity than RSV. The presence of trifluoromethyl group together with a chlorine atom increased the antioxidant activity compared to RSV.

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents

“…However, the poor bioavailability and the high metabolic rate of RSV require the identification of new compounds with optimized structures. In previous studies, we have shown that the substitution of the 4-position on the aromatic ring of RSV with groups with different electronic and lipophilic properties improved their biological activity [35][36][37][38]. Most of the compounds studied here were tested for their antioxidant activity, and a correlation between the presence of 3 -chlorine and an improved scavenger ability of 4 -hydroxyl [38] was proven.…”

“…In previous studies, we have shown that the substitution of the 4-position on the aromatic ring of RSV with groups with different electronic and lipophilic properties improved their biological activity [35][36][37][38]. Most of the compounds studied here were tested for their antioxidant activity, and a correlation between the presence of 3 -chlorine and an improved scavenger ability of 4 -hydroxyl [38] was proven. Research conducted using HPLC showed that most of the compounds tested in this study had values of Log P higher than those of RSV [38].…”

“…In our ongoing study on the structural optimization of RSV, we focused on the R 2 and R 4 groups in the new scaffold and maintained the 4 -OH group on ring B (Figure 1) due to its well-documented role in antioxidant activity [33,34]. We started from the evidence that the introduction of a substituent with different electronic and lipophilic properties at the 4-position on the aromatic ring A (R 3 ) (Figure 1) improved the anticancer, antibacterial, and antioxidant activities [35][36][37][38].…”

“…The synthesis of compounds 1-11 was carried out following the reported route [35,38]. The new compounds, compounds 12-13, were obtained as shown in Figure 2.…”

Design, Synthesis and Biological Evaluation of Aromatase Inhibitors Based on Sulfonates and Sulfonamides of Resveratrol

“…To enlarge the biological potential of RSV derivatives, and to ameliorate the pharmacokinetic profile, the hydroxy groups in the 3 and 5 positions were substituted with hydrogens and different functional groups were inserted in the 4'-position. These RSV derivatives with low molecular weight and better solubility were tested for their different bioactivities [49][50][51]. Starting from these premises, we herein surmise that the removal the 3,5-dihydroxy moiety and the anchoring a sulfonamide or sulfonate linker on the 4'-OH of RSV could improve its anticancer activity as well as chemical stability.…”