Resveratrol derivatives: Synthesis and their biological activities

Resveratrol, a natural compound known especially for its antioxidant properties and protective action, opens the door for both it and its structural derivatives to be considered not only as chemopreventive but also as cancer chemotherapeutic agents. Due to the pharmacokinetic problems of resveratrol that demonstrate its poor bioavailability, the study of new derivatives is of interest. Thus, in this work (E)-stilbenes derived directly from resveratrol and other cyclic analogues containing the benzofuran or indole nucleus have been synthesized. The synthesized compounds have been evaluated for their ability to affect tumor growth in vitro. Compounds 2, 3, 4 and 5 have shown cytotoxicity in human colon cancer (HT-29) and human pancreatic adenocarcinoma cells (MIA PaCa-2) higher than those of (E)-resveratrol. The indolic derivative 13, a cyclic analog of resveratrol, has shown in vitro cytotoxic activity 8 times higher than resveratrol against HT-29 cancer cells. The cyclic derivatives 8, 9 and 12 showed a high inhibition of cell growth in HCT-116 (KRas mutant) at 20 μM, while 13 shows moderate antiangiogenesis activity at 10 μM. [Display omitted] •A series of resveratrol derivatives has been synthesized.•Compounds 2, 3, 4, 5, 8, 9, 10 and 13 have greater cytotoxicity than resveratrol.•8 and 9 show better neuroprotective effect than resveratrol.•Resveratrol derivatives present a multi-target profile.