This review describes the evolution of synthetic methods towards 1,4-benzodioxane lignan natural products, from early biomimetic approaches to recent enantiospecific syntheses. Additionally, a comprehensive report of their biosynthesis and significant biological activities is detailed.

The thieno[2,3-b]pyridines bind to TDP1 with the best analogue 9d with IC₅₀ at 0.5 μM.

Biological thiols (biothiols) in cells and bodily fluids are intrinsically linked to the functioning of important enzymes, deficiency of which can lead to a wide range of physiological and pathological conditions. Therefore, biothiol analysis is crucial for monitoring health and diseases in humans. Herein, we present the synthesis of a novel conducting polymer, poly(EDOT-thioacetate-co-EDOT) and its use in the development of an electrochemical detection platform for biological thiols, exemplified by detection of glutathione (GSH). The detection principle is based on electrochemical conversion of the thioacetate moieties on the conducting polymer to thiols which can form disulfide bonds with GSH present via electrochemical oxidation. Differential pulse voltammary (DPV) was used to generate the sensor readout where the signal corresponds to electrochemical oxidative coupling of GSH to the thiol moiety on the polymer. The sensor response of the optimised sensor has a proportional relationship with the logarithm of GSH concentrations between 1 μM and 600 μM, with a limit of detection of 0.32 μM. The optimised sensor also has an excellent selectivity regarding common bodily fluids-present interfering agents, such as uric acid, glucose, NaCl and KCl. The poly(EDOT-thioacetate-co-EDOT) also demonstrated the excellent re-usability and repeatability for detection of GSH up to the tested 10 cycles. The develop sensor platform is the first in its class and is an extremely promising method for the rapid, selective and sensitive detection of a range of important biological thiols using a simple electrochemical readout.

The physicochemical properties of classical lignans, neolignans, flavonolignans and carbohydrate-lignan conjugates (CLCs) were analysed to assess their ADMET profiles and establish if these compounds are lead-like/drug-like and thus have potential to be or act as leads in the development of future therapeutics. It was found that while no studied compounds were lead-like, a very large proportion (>75%) fulfilled all the requirements to be deemed as present in drug-like space and almost all compounds studied were in the known drug space. Principal component analysis was an effective technique that enabled the investigation of the relationship between the studied molecular descriptors and was able to separate the lignans from their sugar derivatives and flavonolignans, primarily according to the parameters that are considered when defining chemical space (i.e., number of hydrogen bond donors, acceptors, rotatable bonds, polar surface area and molecular weight). These results indicate that while CLCs and flavonolignans are less drug-like, lignans show a particularly high level of drug-likeness, an observation that coupled with their potent biological activities, demands future pursuit into their potential for use as therapeutics.