Resveratrol, a naturally occurring phenolic stilbene molecule, has been intensively researched for its anti-inflammatory, anticancer, antioxidant, antibacterial, and neuroprotective properties. However, due to its limited absorption and probable hepatotoxicity, it is difficult to employ directly as a medication, limiting its therapeutic applicability. Over the last five years, numerous structural changes in resveratrol have been widely studied, resulting in considerable improvements in pharmacological activity and drug availability. This work reviews the biological activities and structure–activity relationships (SARs) of resveratrol derivatives, with the goal of providing useful insights for the discovery of new resveratrol derivatives.

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.

It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, a total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel 17β-HSD10 inhibitors based on rational design and SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC₅₀ = 1.65 ± 0.55 μM) and low toxicity (HepaRG IC₅₀ >100 μM). The Morris water maze experiment revealed that compound 33 could alleviate cognitive impairment induced by scopolamine in mice. This study facilitates the further development of more potent 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.

The pyrin domain-containing protein 3 (NLRP3) inflammasome may be a potential target for the treatment of inflammatory bowel disease (IBD), and inhibiting the activation of the NLRP3 inflammasome is of great significance for the treatment of IBD. In this study, 27 novel chalcone derivatives were designed and synthesized. Enzyme-linked immunosorbent assay (ELISA) analysis revealed that most of the compounds inhibited IL-1β secretion, with F14 exhibiting the most significant activity, showing IC₅₀ values of 0.74 μM (mouse bone marrow-derived macrophage, BMDM) and 0.88 μM (Tohoku Hospital Pediatrics-1, THP-1), respectively. Flow cytometry and immunofluorescence analysis revealed that F14 had no effect on mitochondrial reactive oxygen species (ROS) production or mitochondrial damage, nor did it affect the expression of key protein components of the NLRP3 inflammasome. Western blot and computational docking studies suggested that F14 may exert anti-inflammatory activity by targeting NLRP3 to block the oligomerization and speck formation of ASC protein. In vivo studies demonstrated that F14 exhibited significant therapeutic effects on dextran sulfate sodium (DSS)-induced acute colitis in mice. Overall, this work provides candidate compounds for the development of NLRP3 inflammasome inhibitors and the treatment of inflammatory diseases caused by NLRP3 inflammasome activation.

In recent years, phthalide and pterostilbene have been widely studied as important natural products.