Isolation of Anti-SARS-CoV-2 Natural Products Extracted from Mentha canadensis and the Semi-synthesis of Antiviral Derivatives.

Traditional herbal medicine offers opportunities to discover novel therapeutics against SARS-CoV-2 mutation. The dried aerial part of mint (Mentha canadensis L.) was chosen for bioactivity-guided extraction. Seven constituents were isolated and characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Syringic acid and methyl rosmarinate were evaluated in drug combination treatment. Ten amide derivatives of methyl rosmarinate were synthesized, and the dodecyl (13) and 3-ethylphenyl (19) derivatives demonstrated significant improvement in the anti-SARS-CoV-2 plaque reduction assay, achieving IC50 of 0.77 and 2.70 µM, respectively, against Omicron BA.1 as compared to methyl rosmarinate's IC50 of 57.0 µM. Spike protein binding and 3CLpro inhibition assays were performed to explore the viral inhibition mechanism. Molecular docking of compounds 13 and 19 to 3CLpro was performed to reveal potential interaction. In summary, natural products with anti-Omicron BA.1 activity were isolated from Mentha canadensis and derivatives of methyl rosmarinate were synthesized, showing 21- to 74-fold improvement in antiviral activity against Omicron BA.1.

Doubled production of cordycepin analogs in cultured Cordyceps militaris by addition of Andrea droppings.

Cordyceps sinensis is a traditional Chinese medicine with various biological activities. With its limited natural supply, cultured C. militaris has become the major alternative source, and the culture conditions may affect the chemical compositions. To improve the production of chemical ingredients, C. militaris was cultured with three different media, including rice only, rice plus 3% tea leaves, and rice plus 3% droppings of Andraca theae. The fractions of dried C. militaris cultured with rice were chromatographic separated to afford ten compounds: phenylalanine, dimerumic acid, nicotinic acid, tryptophan, N6-(2-hydroxyethyl)-adenosine, uracil, uridine, cordycepin, ergosterol, and mannitol. Of these, in the cultured medium of rice plus 3% Andraca droppings, the amount of one major compound cordycepin is about two folds than the highest reported data, and dimerumic acid and N6-(2-hydroxyethyl)-adenosine were isolated for the first time from this species.[Figure: see text].

Chemical investigation on the root bark of Bombax malabarica.

Ten compounds were isolated from the root bark of Bombax malabarica, including two new compounds, bombamalin (1) and 3,4,5-trimethoxyphenol-1-[ß-xylopyranosyl-(1 → 2)]-ß-glucopyranoside (3), and shorealactone (4), a rare dehydroascorbic acid fused l-ε-viniferin. Compound 1 is an unusual bissesquiterpene, containing a 1,4-dioxene ring formed by fusing isohemigossypol with ent-cadinen-2-one. Their structures were elucidated by extensive spectroscopic analysis. This chemical reinvestigation is of value for chemotaxonomy of the Bombax genus, in particular the finding of the unusual 1 and rare 4. Among the isolates, shorealactone (4), l-epicatechin 5-O-ß-D-xyloside (5), and 2-C-[ß-D-apiosyl-(1 → 6)]- ß-D-glucosyl]-1,3,6-trihydroxy-7-methoxyxanthone (6) displayed some inhibition against α-glucosidase with IC50 values of 224, 345, and 285 µM, respectively.

Chemical investigation of Hyptis suaveolens seed, a potential antihyperuricemic nutraceutical, with assistance of HPLC-SPE-NMR.

The seed of Hyptis suaveolens, commonly known as wild flour ball (san fen yuan) in Taiwan, serves as a main refreshing drink substance in several regions. This study investigated firstly its secondary metabolites, leading to the isolation of five major caffeoylquinic acid derivatives (1-5) from the ethanol extract. In addition, ten minors, including three caffeoylquinic acid derivatives (12-14), were characterized via assistance of HPLC-SPE-NMR. Of these isolates, sodium 4,5-dicaffeoylquinate (2) and methyl 3,5-dicaffeoylquinate (4) showed moderate inhibitory activity against xanthine oxidase with the respective IC50 values of 69.4 µM and 92.1 µM (c.f. allopurinol IC50 28.4 µM). Quantitative HPLC analysis of the EtOH extract indicates the content of sodium 3,5-dicaffeoylquinate (1) and sodium 4,5-dicaffeoylquinate (2) to be 0.1% and 0.08% (w/w, dry seed), respectively. This study not only discloses the bioactive constituents, but also demonstrates the potential of H. suaveolens seed as an antihyperuricemic nutraceutical.

Cytotoxic protobassic acid saponins from the kernels of Palaquium formosanum.

Bioassay guided fractionation and separation of the EtOH extract of the kernels of Palaquium formosanum against PC-3 cells via Sephadex LH-20 and reverse phase C-18 columns led to the isolation of 13 protobassic saponins. One of these saponins is new and was characterized as 3‴-O-rhamnopyranosyl-arganin C, a bisdesmoside of 16α-hydroxyprotobassic acid at the C-3 and C-28 positions. The structures of these compounds were determined on the basis of 1D NMR (1H, 13C), 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY), and selectively excited 1D TOCSY spectroscopic analyses and MS data, and comparison with literature data. Bioassay of these compounds and five additional compounds, isolated from Planchonella obovata leaf, against PC-3 prostate cancer cells indicated arganin C to be the most potent one with the IC50 value of 13.8 µM. Some structure and activity relationships were also drawn.

A Novel 3,4-Secocycloartane Triterpene, Bearing a Tetrahydropyran Moiety, from Pasaniaformosana Leaf.

Bioassay guided fractionation against a-glucosidase and separation of the ethanolic extract of Pasania formosana leaf by chromatographic methods led to the isolation of a novel secocycloartane triterpene. This compound, named pasasecocycloartenoic acid, was elucidated as 21,24(R)-epoxy-25-hydroty-3;4- secocycloart-4(28)-en-3-oic acid through analysis of 1D and 2D NMR spectra and on the basis of HRESIMS data. The compound showed weak activity against α-glucosidase, but its poor solubility hampered the bioassay.

Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.

Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (-)-actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyactinodaphnine (9) are new aporphines, although (+)-2 and (±)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 µM, respectively.

Flavonoids from Curcuma longa leaves and their NMR assignments.

Chemical investigation of the n-BuOH-soluble fraction of the EtOH extract of the aerial part of Curcuma longa led to the isolation of 11 flavonol glycosides and one dihydroflavonol glucoside (1) via chromatography over Sephadex LH-20 and Lobar RP-18 columns. Although they are known, the 1H and 13C NMR data recorded in CD3OD rather than the common DMSO-d6 are doubly checked via extensive 2D NMR spectroscopic analyses, leading to some revisions of the reported data, especially for the glycon part.

Neolignans as xanthine oxidase inhibitors from Hyptis rhomboides.

The active fraction from the EtOH extract of Hyptis rhomboides against xanthine oxidase was identified by use of an HPLC microfractionation-centrifugal vacuum evaporation-bioassay hyphenated technique. Scale-up separation of the active subfractions using semi-preparative RP-HPLC provided 13 phenylpropanoid compounds, including O-styrenylneolignans, hyprhombins A-C, epihyprhombin B, and hyprhombin B methyl ester, and O-caffeoylnorneolignans, hyprhombins D and E. All of these compounds shared a common 1,4-benzodioxane skeleton, as established by spectroscopic analyses. Hyprhombin C and epihyprhombin B exhibited better anti-xanthine oxidase activity than allopurinol, with IC50 values of 0.6 and 2.0 µM, respectively.

Triterpenes as α-glucosidase inhibitors from Fagus hayatae.

Triterpenoids, 1-3, 8 and 9, along with 24 known compounds were isolated from leaves and twigs of Fagus hayatae. Of these, compound 1, 1,10-seco-3ß,10α,23-trihydroxyolean-12-ene-1,28-dioic acid 1,23-lactone, possesses a hitherto unknown 1,10-seco-oleanane skeleton. In addition, 2,3-seco-20(29)-lupene-2,3-dioic acid (16), previously described as a synthetic product, is now established as a plant natural product; the neolignan-9'-O-rhamnoside 19 is also characterized herein. Their structures were deduced mainly by 1D and 2D NMR spectroscopic analyses. Seven of these compounds possess moderate inhibitory activity against α-glucosidase type IV (Bacillus stearothermophilus).

Characterization of Acetylcholinesterase Inhibitory Constituents from Annona glabra Assisted by HPLC Microfractionation.

The active fraction of the EtOH extract of the stem of Annona glabra against acetylcholinesterase (AChE) was analyzed by combining HPLC microfractionation with a bioassay. The analytical-scale sample was fractionated by HPLC-DAD into 96-well microplates, which, after evaporation, were assayed against AChE. The active subfractions were scaled up by separation over semipreparative HPLC to give 20 compounds. Four of these, (7S,14S)-(-)-N-methyl-10-O-demethylxylopinine salt (3), S-(-)-7,8-didehydro-10-O-demethylxylopininium salt (10), S-(-)-7,8-didehydrocorydalminium salt (11), and 5-O-methylmarcanine D (17), were assigned as new natural products. In addition, compounds 10 and 11 represent the first natural occurrence of 7,8-didehydroprotoberberines. Compound 3, pseudocolumbamine (12), palmatine (15), and pseudopalmatine (16) showed anti-AChE IC50 values of 8.4, 5.0, 0.4, and 1.8 µM, respectively.