Selective Reduction of the Exomethylene Group of α-Methylene γ- or δ-Lactones with CdCl2–Mg–MeOH–H2O‡

Bhattacharya, Asish K.; Jain, D. C.; Sharma, Ram Prakash

doi:10.1039/a803981j

Cited by 6 publications

(2 citation statements)

References 7 publications

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“…Fraction 1 contained mostly methyl linoleate (Figure , 1 ). Six sesquiterpenoids were isolated from fraction 2, which had bioactivity against glioblastoma: a MeOH adduct of arteannuin B ( 2 ), which has been previously reported without NMR data, , artemisinin ( 3 ), epi -deoxyarteannuin B ( 4 ), artemisinic acid ( 5 ), arteannuin B ( 6 ), and dihydroartemisinic acid ( 7 ). Out of all of the compounds isolated in fraction 2, isocoumarin ( 8 ) was the most abundant based on the proton NMR spectrum of this fraction.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

et al. 2023

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Artemisia annua is the plant that produces artemisinin, an endoperoxide-containing sesquiterpenoid used for the treatment of malaria. A. annua extracts, which contain other bioactive compounds, have been used to treat other diseases, including cancer and COVID-19, the disease caused by the virus SARS-CoV-2. In this study, a methyl ester derivative of arteannuin B was isolated when A. annua leaves were extracted with a 1:1 mixture of methanol and dichloromethane. This methyl ester was thought to be formed from the reaction between arteannuin B and the extracting solvent, which was supported by the fact that arteannuin B underwent 1,2-addition when it was dissolved in deuteromethanol. In contrast, in the presence of N-acetylcysteine methyl ester, a 1,4-addition (thiol-Michael reaction) occurred. Arteannuin B hindered the activity of the SARS CoV-2 main protease (nonstructural protein 5, NSP5), a cysteine protease, through time-dependent inhibition. The active site cysteine residue of NSP5 (cysteine-145) formed a covalent bond with arteannuin B as determined by mass spectrometry. In order to determine whether cysteine adduction by arteannuin B can inhibit the development of cancer cells, similar experiments were performed with caspase-8, the cysteine protease enzyme overexpressed in glioblastoma. Time-dependent inhibition and cysteine adduction assays suggested arteannuin B inhibits caspase-8 and adducts to the active site cysteine residue (cysteine-360), respectively. Overall, these results enhance our understanding of how A. annua possesses antiviral and cytotoxic activities.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

et al. 2023

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“…Attempts were made to selectively reduce this group using a variety of standard methods; all failed to afford the requisite product, with multiple products forming as a result of concomitant ester hydrolysis and/or epoxide ring opening. Selective reduction was finally achieved by using a metal salt-metal reduction system, namely, cadmium chloride-magnesium in methanol/water (22), which afforded a single diastereomeric product. Analysis by ESI(+)-LC-MS confirmed the addition of 2 mass units, and reaction at the R-methylenebutyrolactone group was established by extensive analysis of the 1 H and 13 C NMR spectra.…”

Section: Resultsmentioning

confidence: 99%

Inactivation of the Cytotoxic Activity of Repin, a Sesquiterpene Lactone from Centaurea repens

Tukov

Anand

Gadepalli

et al. 2004

Chem. Res. Toxicol.

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Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell line have led to the identification of one of several putative agents, which may contribute to ENE, namely, the sesquiterpene lactone (SQL) repin (1), previously linked to ENE due to its abundance in C. repens. To characterize the molecular basis of repin-induced neurotoxicity, the present study was designed to identify reactive functional groups that may contribute overall to its toxicity. The reaction of repin (1) with glutathione (GSH) led to the exclusive addition of GSH to the alpha-methylenebutyrolactone affording a GSH conjugate (3b) that lacked toxicity in the PC12 cell assay, while selective reduction of the alpha-methylenebutyrolactone double bond of 1 also resulted in an analogue (2) that was devoid of toxicity relative to the parent compound. Unlike repin, analogue 2 failed to decrease cellular dopamine levels in PC12 cells, further substantiating the requirement of the alpha-methylenebutyrolactone group. Results from this study are suggestive that GSH depletion by the SQL repin may be a primary event in the etiology of ENE, increasing the susceptibility to oxidative damage.

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ChemInform Abstract: Selective Reduction of the Exomethylene Group of α‐Methylene γ‐ or δ‐Lactones with CdCl₂—Mg—MeOH—H₂O.

Bhattacharya¹,

Jain²,

Sharma³

1999

ChemInform

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Selective Reduction of the Exomethylene Group of α-Methylene γ- or δ-Lactones with CdCl2–Mg–MeOH–H2O‡

Cited by 6 publications

References 7 publications

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

Inactivation of the Cytotoxic Activity of Repin, a Sesquiterpene Lactone from Centaurea repens

ChemInform Abstract: Selective Reduction of the Exomethylene Group of α‐Methylene γ‐ or δ‐Lactones with CdCl₂—Mg—MeOH—H₂O.

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Selective Reduction of the Exomethylene Group of α-Methylene γ- or δ-Lactones with CdCl2–Mg–MeOH–H2O‡

Cited by 6 publications

References 7 publications

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B

Inactivation of the Cytotoxic Activity of Repin, a Sesquiterpene Lactone from Centaurea repens

ChemInform Abstract: Selective Reduction of the Exomethylene Group of α‐Methylene γ‐ or δ‐Lactones with CdCl2—Mg—MeOH—H2O.

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ChemInform Abstract: Selective Reduction of the Exomethylene Group of α‐Methylene γ‐ or δ‐Lactones with CdCl₂—Mg—MeOH—H₂O.