Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1′P-oriented atropisomers showed much more significant antiviral potency than their corresponding 1′M-oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.

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Cancer is a leading cause of mortality in the world and metastasis is to blame. Invasion is the initial step of metastasis. Therapies targeting epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling pathways can reduce stemness of cancer cells and thus inhibit cancer invasion. A large number of anti-cancer naphthoquinones (NQs) can target cancer invasion by acting on EMT, CSCs and STAT3 signaling. Furano-naphthoquinones (FNQs) belong to a class of NQ derivatives commonly characterized by a naphthoquinone fused with a furano ring. A study indicated that the corporation of the furano ring improved the anticancer potency as compared to the other classes of NQs. BBI608, a natural FNQ, which can be found in the woods or barks of several Tabebuia species, has entered phases I and II clinical trials. It has been regarded as a potential candidate for new-generation lead compound acting directly on CSCs to overcome the chemotherapy resistance. Apart from the natural plant sources, there are a number of synthetic FNQ derivatives that are effective in reducing stemness of cancer cells and thus are anti-invasive. In this review, the anti-invasion mechanisms of NQs and the more powerful FNQs, together with their natural origins, synthetic derivatives as well as their synthetic routes are discussed.

Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((−)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.

One of the structural uniqueness of arylnaphthalene lignans (ANLs) is their potential atropoisomerism, which may result in bioactivity discrepancy. However, the stable ANL atropisomers rarely exist in nature. In the course of our phytochemical study of Justicia procumbens, we isolated nine ANL glycosides (1-9) with four of them (1-4) being identified as new stable atropisomers. Their absolute configurations were determined based on the analysis of the circular dichroism (CD) and electronic circular dichroism (ECD) data.The ANL compounds were evaluated for their antiviral potential as entry inhibitors against the infections of H5N1 influenza virus, vesicular stomatitis virus (VSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 5 being the most potent one with IC 50 values ranging from 0.0063-1.13 μM. The atropisomers did not display significant antiviral activity, indicating that a free rotation of the biphenyl aryl-aryl bond could play a significant role in the antiviral activity of ANL compounds.