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Three nor-sesquiterpenes, phellinharts A–C (1–3), isolated from Phellinus hartigii, exhibited unprecedented protoilludane and cerapicane-type structures. The structures of compounds 1–3were elucidated via spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Potential biogenic pathways involving demethylation, ring cleavage, and rearrangement were proposed. Compounds 1–3displayed potent anti-hypertrophic activities with low cytotoxicity (CC50> 50 μM) in rat cardiomyocytes, underscoring their therapeutic potential.

Three new rearranged diterpenoids, strophioblachins A–C (1–3), eight new diterpenoids, strophioblachins D–K (4–11), and seven previously described diterpenoids (12–18) were purified from the aerial parts of Strophioblachia fimbricalyx.Compounds 1and 2contain a rare 6/6/5/6 ring system, while 3has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1–11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11and 9. The absolute configurations of compounds 1, 3, and 10were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10and 15dose-dependently lowered the mRNA expression of Nppaand Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10and 15lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10and 15were only very weakly active in the range.

Callintegers A (1) and B (2), unprecedented clerodane norditerpenoids based on a novel carbon skeleton, were isolated from Callicarpa integerrima. Compounds 1and 2possess a novel 6/6/6-fused tricyclic ring system. Their structures and absolute configurations were determined by quantum chemical calculations, spectroscopic analysis, and single-crystal X-ray diffraction methods. Biological evaluation showed that compound 2inhibited IL-1β secretion in a dose-dependent manner with an IC50value of 5.5 ± 3.2 μM. Caspase-1 maturation and IL-1β secretion were also reduced, indicating that compound 2impaired NLRP3 inflammasome activation.

Eight new aspulvinone analogues, aspulvins A–H (1–8) and aspulvinones D, M, O, and R (9–12), were isolated from cultures of the endophytic fungus Cladosporiumsp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 μM. Notably, compounds 9, 10, and 12showed potential SARS-CoV-2 Mproinhibition with IC50values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 μM, respectively. For all compounds except 3and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50values ranging from 0.7 to 7.4 μM. Compound 10showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1β maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

A spiro ent-clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (1), together with four new monomeric analogues (2–5), were isolated from Callicarpa arborea. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC50value of 7.3 μM. This gave a KDvalue of 5.0 μM, as recorded by a surface plasmon resonance binding assay.

A phytochemical study on the aerial parts of Leonurus japonicusled to the isolation and identification of 38 labdane diterpenoids, including 18 new (1, 2, 11, 12, 16–21, 24, 30–34, 37, 38) and 20 known (3–10, 13–15, 22, 23, 25–29, 35, 36) analogues. Their structures were elucidated based on physical data analysis, including 1D and 2D NMR, HRMS, UV, IR, and X-ray diffraction. The structure of the known compound 4was confirmed by single-crystal X-ray diffraction data. These compounds can be divided into furanolabdane (1–10), tetrahydrofuranolabdane (11–15), lactonelabdane (16–23), labdane (24–29), and seco-labdane (30–38) type diterpenoids. All compounds were screened by lipopolysaccharide (LPS)-induced nitric acid (NO) production in RAW264.7 cells to evaluate anti-inflammatory effects. Compounds 1, 5, 10–13, 16–19, 31–33, and 38inhibited NO production with IC50values lower than 50 μM, with compound 30being the most active, with an IC50value of 3.9 ± 1.7 μM. Further studies show that compound 30inhibits pro-inflammatory cytokine production and IKK α/β phosphorylation and restores the IκB expression levels in the NF-κB signaling pathway.

Callicarpins A–D (1–4), possessing an unprecedented A-homoent-clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E–G (5–7), with 5/6-fused ent-clerodane diterpenoid skeletons, were isolated from Callicarpaarboreaand C. integerrim. Their structures were elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, and electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these callicarpins are proposed. Compounds 2, 3b, and 6–8showed potent inhibitory effects against the NLRP3 inflammasome with IC50values from 1.4 to 5.3 μM, and 2significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.

Species belonging to the genus Callicarpaare used traditionally in Chinese medicine for the treatment of inflammation, rheumatism, and pain. Investigation of the leaves and twigs of Callicarpa bodinieriresulted in the isolation of nine new abietane diterpenoids, bodinieric acids A–I (1–9), along with six known compounds (10–15). The structures of 1–9were elucidated on the basis of the interpretation of their HRESIMS and NMR data and by ECD calculations. To explore the potential therapeutic target of this plant for immune-mediated disease, the inhibitory activities of the isolates obtained were determined against 13 kinase enzymes. Eight compounds exhibited moderate inhibitory effects on spleen tyrosine kinase (SYK), and the IC50values of compounds 2and 6were 7.2 and 10.7 μM, respectively. In addition, a preliminary structure–activity relationship of this scaffold was analyzed with both molecular docking and a 3D-QSAR pharmacophore model.

Ten new ingol lathyrane-type diterpenes (1−10) and two known ingenol derivatives (11and 12) were isolated from the aerial parts of Euphorbia royleana. The structures of 1−10were elucidated on the basis of spectroscopic methods including 2D NMR analysis, and the structure of compound 1was confirmed by single-crystal X-ray crystallography. Antiangiogenic effects of all compounds except for 5were tested using a zebrafish model, with compounds 11and 12being active in this bioassay.

Investigation of an organic extract of Schisandra rubrifloraled to the isolation of three new highly oxygenated nortriterpenoids, named rubriflorins A−C (1−3), together with six related known compounds (4−9). Their structures were elucidated by spectroscopic evidence. Compounds 1−3feature the opening of ring A compared with related known nortriterpenoids isolated from the genus Schisandraand showed anti-HIV-1 activities with EC50values of 10.0, 16.2, and 81.3 g/mL, respectively.

Six new nortriterpenoids, lancifodilactones I−N (1−6), as well as nine known ones, were isolated from the leaves and stems of Schisandra lancifolia. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR analysis, and the structures of compounds 1 and 4 were further confirmed by single-crystal X-ray crystallography. In addition, all new compounds were tested for anti-HIV-1 activity.

Two new taxoids, 13,15-epoxy-13-epi-taxayunnasin A (1) and taxchinin N (2), were isolated from the leaves and stems of Taxus chinensis. Compound 2is the first taxoid to be reported with an ,-unsaturated lactone at C-4, C-5, C-20, and C-2. The structure of 1was elucidated by spectroscopic analysis and confirmed by semisynthesis from taxayunnasin A, while 2was determined structurally using spectroscopic methods and by single-crystal X-ray diffraction.