Synthesis and antihepatoma activity of guaianolide dimers derived from lavandiolide I.

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.

Artemannuols A-C, novel sesquiterpenoid-flavonol hybrids with antihepatoma activity from Artemisia annua.

Artemisia annua, also known as "Qinghao" in Chinese, is a famous traditional Chinese medicine and has been used for the treatment of malaria and various tumors. In this study, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and elucidated by extensive spectral data and ECD calculations. Structurally, artemannuols A-C (1-3) are the first examples of sesquiterpenoid-flavonol hybrids fused by an ether bond, among which artemannuols A and B (1 and 2) are composed of bisabolane-type sesquiterpenoid and flavonol moieties, and artemannuol C (3) is composed of humulane-type sesquiterpenoid and flavonol moieties. The antihepatoma assay suggested that compounds 1-3 showed inhibitory effects against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values in the range of 32.7 to 70.4 µM.

Artemongolides A-F, undescribed sesquiterpenoid dimers from Artemisia mongolica and their antihepatic fibrosis activities.

Artemongolides A-E (1-5), an unusual class of diseco-guaianolides featuring a rare fused 7-methylbicyclo[2.2.1]-2-ene-7-heptanol ring system, and artemongolide F (6), the first example of [4 + 2] Diels-Alder type adducts presumably incorporating a chain farnesane sesquiterpene and a guaianolide diene, were isolated from the whole plant of Artemisia mongolica. Their structures were elucidated based on the spectroscopic analyses of UV, IR, MS, and 1D and 2D NMR spectra. The absolute configurations of artemongolides A (1) and F (6) were determined by single-crystal X-ray crystallography, and those of artemongolides B-E (2-5) were established by ECD calculations. Cytotoxicity evaluation suggested that compound 1 exhibited activity against HSC-LX2 cells with an IC50 value of 165.0 µM, equivalent to that of the positive control silybin (IC50, 146.4 µM). Preliminary mechanism studies revealed that compound 1 could inhibit the deposition of human collagen type I (Col I), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 123.8, 160.4, and 139.20 µM.

Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents.

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.

Artemzhongdianolides A1-A21, antihepatic fibrosis guaiane-type sesquiterpenoid dimers from Artemisia zhongdianensis.

In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 µg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 - A21 (1-21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1, 13, and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC50 values ranging from 14.0 to 95.2 µM. Of them, compounds 2, 6, and 13 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 22.1, 24.3 and 14.0 µM, which were 6 to 10 times more active than the positive drug silybin (IC50, 148.6 µM). Preliminary mechanism study revealed that compounds 2, 6, and 13 could markedly inhibited the deposition of human collagen type Ⅰ (Col Ⅰ), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 37.9, 54.8, and 28.0 µM (Col Ⅰ), 29.5, 25.3, and 42.9 µM (HL), 31.2, 94.6, and 12.4 µM (HA), which were 1.5 to 13-fold more potent than silybin.

New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai.

Ten new diarylheptanoid dimers, katsumadainols C1 - C10 (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 µM) and 117.8-348.2% (12.5 µM). Compounds 1-4 exhibited significant inhibition on GPa with IC50 values of 18.0-31.3 µM; compounds 1-5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9-18.2 µM; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 µM. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma.

Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC50 values of 32.7 and 34.3 µM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract.

Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol derivatives as α-glucosidase and PTP1B inhibitors.

The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on α-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 µM. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their α-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 µM (α-glucosidase) and 319.7, 269.1 µM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC50 value of 134.9 µM, which was 2.5-fold higher than the positive control, suramin sodium (IC50 339.0 µM), but not inhibit α-glucosidase.

Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants.

The antidepressant activity of (+) and (-)-paeoveitol was first evaluated using the forced swimming test (FST), and (+)-paeoveitol showed potential antidepressant activity by decreasing immobility time of mice (by approximately 26.4%) in the FST at a dose of 20 mg/kg. To explore the structure-activity relationships (SARs) and obtain more potent compounds, twenty derivatives of (+)-paeoveitol were synthesized and evaluated for their agonistic activities on melatonin type I (MT1) and type II (MT2) receptors. As a results, compound 13 with an N-methylpiperazine fragment exhibited obvious effect on MT1 and MT2 receptors with EC50 values of 0.20 and 0.24 mM. Moreover, compound 13 dose-dependently decreased the immobility of mice in the FST and showed an inverted U-shaped dose-effect, and the most efficacious dose (at 40 mg/kg) was comparable to fluoxetine (20 mg/kg) with a reduced immobility time of 29.2% and 34.5%, respectively. In vivo neurochemical assays suggested that compound 13 obviously increased 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) levels in the mice brain, indicating that its antidepressant effects might be related to the monoaminergic system. In silico ADMET study revealed that 13 has favorable pharmacokinetic properties. These findings suggest that compound 13 could be a potential antidepressant agent. Graphical abstract.

Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2.

Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 µM. To explore the structure-activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25-27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 µM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 µM.

Artemicapillasins A-N, cytotoxic coumaric acid analogues against hepatic stellate cell LX2 from Artemisia capillaris (Yin-Chen).

Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 µg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A-N (1-14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 µM. The most active artemicapillasin B (2) gave an IC50 value of 24.5 µM, which was about 7 times more toxic than the positive drug silybin (IC50, 162.3 µM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC50 values of 11.0, 14.4 and 13.8 µM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study.

Diarylheptanoid-chalcone hybrids with PTP1B and α-glucosidase dual inhibition from Alpinia katsumadai.

The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A1-A16 (1-16), together with 13 known analogues (17-29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1-3, 5-7, 11-14, 21-25, and 27 showed PTP1B/TCPTP selective inhibition with IC50 values ranging from 22.0 to 96.7 µM, which were 2-10 times more active than sodium orthovanadate (IC50, 215.7 µM). All compounds exhibited obvious inhibition against α-glucosidase with IC50 values of 2.9-29.5 µM, indicating 6-59 times more active than acarbose (IC50, 170.9 µM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with Ki values of 13.1, 12.9, 21.6 µM, and 4.9, 7.4, 3.4 µM, respectively.

Artematrovirenins A-P, guaiane-type sesquiterpenoids with cytotoxicities against two hepatoma cell lines from Artemisia atrovirens.

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.

Artatrovirenols A and B: Two Cagelike Sesquiterpenoids from Artemisia atrovirens.

Artatrovirenols A and B (1 and 2), two novel cagelike sesquiterpenoids, possess a unique 5/5/6/5/5-pentacyclic and a 5/5/6/5-tetracyclic system with an unprecedented tetracyclo[5.3.1.1.4,1101,5]dodecane scaffold from Artemisia atrovirens. The structures of compounds 1 and 2 including their absolute stereochemistry were elucidated through extensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Plausible biosynthetic pathways for the new isolates were proposed from the naturally occurring arglabin (3) via the key intramolecular Diels-Alder cycloaddition. Compound 1 showed cytotoxicity against three human hepatoma cell lines (HepG2, SMMC-7721, and Huh7) with half maximal inhibitory concentration values of 123.8, 44.0, and 142.6 µΜ, respectively.

Synthesis and biological evaluation of chepraecoxin A derivatives as α-glucosidase inhibitors.

The ent-kaurane diterpenoid chepraecoxin A (CA) obtained in our previous study showed a potential inhibitory activity on α-glucosidase (IC50 274.5 ± 12.5 µM). In order to figure out the structure-activity relationships (SARs), twenty-two derivatives of chepraecoxin A were synthesized by modifying the ester, allyl, double bond and carboxyl groups, and assayed for their α-glucosidase inhibitory activity. Of them, eight compounds (14-17, 19-22) significantly increased activity with IC50 values ranging from 16.1 to 71.4 µM, even higher than the positive control, acarbose (IC50 130.3 µM). Especially, compounds 17, 19 and 21 could inhibit α-glucosidase with IC50 values of 16.9 ± 3.4, 16.1 ± 1.2, and 17.1 ± 0.6 µM, 17-fold higher than CA. The most active compound 19 was proven to be a non-competitive inhibitor with a Ki value of 19.4 µM based on enzyme kinetics study. The primary SARs of CA derivatives were summarized for exploring antidiabetic candidates.

Artemyrianolides A-S, Cytotoxic Sesquiterpenoids from Artemisia myriantha.

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 µg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 µM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 µM (HepG2), 4.3 and 7.8 µM (Huh7), and 3.1 and 9.8 µM (SMMC-7721), respectively.

Spiroseoflosterol, a Rearranged Ergostane-Steroid from the Fruiting Bodies of Butyriboletus roseoflavus.

Spiroseoflosterol (1), a 7(8→9)-abeo-ergostane steroid with a unique spiro[4.5]decan-6-one system, was isolated from the fruiting bodies of Butyriboletus roseoflavus. Its structure was determined by interpretation of comprehensive spectroscopic, X-ray, and computational data. A plausible biogenetic pathway for spiroseoflosterol (1) was postulated based on a key semipinacol rearrangement. Compound 1 was cytotoxic to HepG2 and Huh7/S (sorafenib-resistant Huh7) with IC50 values of 9.1 and 6.2 µM, respectively.

Cytotoxic sesquiterpenoids against hepatic stellate cell line LX2 from Artemisia lavandulaefolia.

The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 µg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC50, 162.3 µM); compounds 6, 9 and 16 showed moderate activity with IC50 values of 109.3, 114.0 and 124.2 µM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 52.1, 16.5 and 21.3 µM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC50 values ranging from 7.3 to 71.6 µM and from 18.6 to 72.9 µM.

Facile synthesis of metal-organic framework-derived SiW12@Co3O4 and its peroxidase-like activity in colorimetric assay.

Over the past few years, artificial enzymes have attracted enormous attention due to their high stabilities and cost-effective productions. In this work, metal-organic framework-derived SiW12@Co3O4 was synthesized in large quantities by stirring the mixture at ambient temperature and calcination. The obtained SiW12@Co3O4 exhibited a highly inherent peroxidase-like activity and excellent stability. Kinetic studies demonstrated that the synthesized SiW12@Co3O4 had a strong binding affinity to 3,3',5,5'-tetramethylbenzidine (TMB), stronger than HRP had. Specifically, the peroxidase-like activity of SiW12@Co3O4 in an aqueous solution was well maintained after incubation at an elevated temperature, at an extreme pH and for a long time. A SiW12@Co3O4-based method was further developed for H2O2 and one-pot glucose detection with good sensitivity and reliability. The facile synthesis approach is expected to facilitate the practical use of metal-organic frameworks and their derivatives as enzyme mimics in the future.