Oxyresveratrol: Structural Modification and Evaluation of Biological Activities

Abstract

Oxyresveratrol (2,4,3 1 ,5 1 -tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic aromatic substitution. The two aromatic rings of the stilbene system of 1 can be chemically modulated by exploiting different protecting groups. Such a strategy allows for selective and exclusive modifications on either ring A or ring B. All compounds were evaluated in vitro for a panel of biological activities, including free radical scavenging activity, DNA protective properties, antiherpetic activity, inhibition of α-glucosidase and neuraminidase, and cytotoxicity against some cancer cell lines. Several derivatives were comparably active or even more potent than the parent oxyresveratrol and/or the appropriate positive controls. The partially etherified analogs 5 1 -hydroxy-2,3 1 ,4-trimethoxystilbene and 3 1 ,5 1 -dihydroxy-2,4-dimethoxystilbene demonstrated promising anti-herpetic and DNA protective activities, offering new leads for neuropreventive agent research, whereas 5 1 -hydroxy-2,3 1 ,4,-triisopropoxystilbene displayed anti-α-glucosidase effects, providing a new lead molecule for anti-diabetic drug development. 3 1 ,5 1 -Diacetoxy-2,4-diisopropoxystilbene showed potent and selective cytotoxicity against HeLa cancer cells, but the compound still needs further in vivo investigation to verify its anticancer potential.

Hepatoprotective potential and chemical characterization of Artocarpus lakoocha fruit extract

“…oxidant, anthelmintic, antiviral, skin whitening, antiproliferative, anti-herpes, insecticidal, inhibition of α-glucosidase and neuraminidase, and cytotoxic activities against different cancer cell lines (Chatsumpun et al, 2016).…”

Effects of oxyresveratrol and its derivatives on cultured P19-derived neurons

“…Compounds 2-4 were prepared from 1 following earlier reported protocols with slight modification [16], as shown in Figure 1. The synthetic route began with the reaction of oxyresveratrol (1) with 2-bromopropane to give di-and tetra-O-isopropyl products (1a and 1b).…”

“…Compounds 2 -4 were prepared through the intermediates 1a -1f, following the previously reported synthetic routes [16].…”

“…and Morus alba L. [6,7]. Our previous studies have shown that 1 possesses a wide range of biological activities, for example, anti-herpetic activity, inhibitory effect on tyrosinase and protective activity against DNA damage [8][9][10]. In recent years, considerable amounts of research have been published on the possible neuroprotective effects of 1.…”

“…The compound was also studied for protective effects against cerebral ischemia in vivo [13], and traumatic injury in vitro [14]. Its antioxidant activity has been investigated in several models [7,15,16].…”