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Solanum mauritianum, commonly known as “Tabaquillo”, was one of the most used plants by tribes from South America as a remedy for headaches. Based on this ethnopharmacological use, a bioguided isolation of compounds with anti-inflammatory and anti-Alzheimer’s activities from S. mauritianum was carried out by measuring the inhibition of NF-κB in C8D1A, Neuro-2a, and EOC 13.31 cells, and by measuring the inhibition of acetylcholinesterase and β-amyloid. This allowed the isolation and characterisation by nuclear magnetic resonance and mass spectrometry of four compounds (1–4). Compounds 1–4 showed NF-κB inhibitory activity with IC50 values of 9.13–9.96, 17.17–17.77, 2.41–2.79, and 1.59–1.93 µM, respectively, while celastrol (the positive control) had an IC50 value of 7.41 µM. Likewise, compounds 1–4 showed anti-Alzheimer’s activity, inhibiting the acetylcholinesterase by 40.33, 20.57, 61.26, and 83.32%, respectively, while galantamine (positive control) showed an inhibition of 90.38%. In addition, concerning the inhibition of β-amyloid aggregation, compounds 1–4 showed an inhibition of 47, 23, 65, and 93%, respectively, while curcumin (positive control) had an inhibition of 71.19%.

Buddleja coriacea Remy is one of the plant species used by the Bolivian population for the treatment of urinary infections. This study aimed to identify the extract, fractions, and compounds responsible for the antibacterial and anti-inflammatory activities of B. coriacea leaves. Bioguided isolation of compounds with antibacterial and anti-inflammatory activities was carried out by measuring the antibacterial effect against specific pathogenic microbial strains, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens, and the inhibition of NF-κB in RM-2 and MM.14Ov cells. Bioassay-guided isolation led to the isolation and characterisation of (4aR,4bS,5 S,6aS,6bS,9aR,10aS,10bS)-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho [2',1':4,5] indeno [1,2-d][1,3] dioxol-2-one (1), 3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl) acrylamide (2), and (1β,11β,12α)-1,11,12-trihydroxy-11,20-epoxypicrasa-3,13(21)-diene-2,16-dione (3) by nuclear magnetic resonance and mass spectroscopy. All compounds showed antibacterial activity with minimum inhibitory concentration values of 11.64–11.81, 0.17–0.19, and 0.34–0.36 µM, respectively, on the tested strains, while the positive control, ofloxacin, had a minimum inhibitory concentration of 27.66 µM. Finally, all the compounds showed NF-κB inhibitory activity with IC50 values of 11.25–11.34, 0.15–0.16, and 0.33–0.36 µM, respectively, in all cell lines, while the positive control, celastrol, had an IC50 of 7.96 µM. Thus, this study managed to isolate and evaluate for the first time the pharmacological potential of three compounds present in the leaves of B. coriacea with antibacterial and anti-inflammatory activities.

Three pentacyclic triterpenes, the oleanolic acid, azarolic acid, and 3-oxo euscaphic acid, were isolated from the hexane extract of Jatropha macrantha Mull.Arg., Euphorbiaceae. The structures of these compounds were elucidated by spectroscopic means. The cytotoxicity of the compounds was evaluated against the THP-1, HEK001, NIH-3T3, and B16-F10 cell lines by the XTT assay. All analyzed compounds were less cytotoxic than the positive control (actinomycin D, CC50 0.00797 μM). The anti-inflammatory activity was evaluated by means of inhibition of NF-κB production and activation of Nrf2 of these compounds against THP-1, HEK001, NIH-3T3, and B16-F10 cell lines. The three compounds had anti-inflammatory activity; however, azarolic acid had a statistically significant higher inhibitory activity of NF-κB production (IC50 1.87–1.98 μM) than the positive control (celastrol, IC50 7.41–7.49 μM). In addition, it had an activation potential of Nrf2 (EC50 2.29–2.85 nM) similar to the positive control (CDDO-Me, EC50 0.11–0.12 nM). The anti-melanogenic activity was evaluated by means of melanin and tyrosinase inhibition of these compounds against the B16-F10 cell line. The three compounds had anti-melanogenic activity; however, azarolic acid was the most active for the inhibition of tyrosinase (IC50 0.95 μM) and inhibition of melanin (IC50 5.21 μM) while the positive control, the kojic acid, had an IC50 of 13.94 μM.

Nineteen N-benzyl linoleamide analogues (macamide from Tropaeolum tuberosum) were synthesised, modifying the molecular structure (benzyl position, aromatic ring and carbonyl group). The structures were confirmed using nuclear magnetic resonance and mass spectrometry techniques. Cell viability and anti-inflammatory activity of these compounds were evaluated in three brain cell lines (C8-D1 A, Neuro-2a, and EOC 13.31). Regarding the effect on NF-κB, several analogues had better inhibition potential than their natural precursor (N-benzyl linoleamide), being the N-(1-(3,5-dimethyl-α-methylbenzyl)-linolethiamide the most active, with IC50 values of 0.01±0.01, 0.01±0.01 and 0.02±0.01 μM, respectively. Finally, all analogues activated Nrf2, with the same compound being the most active, presenting EC50 values of 0.03±0.01, 0.07±0.01 and 0.11±0.02 nM, respectively. Analysing the link between chemical structure and pharmacological activity, our study shows that the changes made to N-benzyl linoleamide lead us to obtaining an analogue with greater anti-inflammatory activity than its precursor and with potential for the treatment of migraine.

Although Tropaeolum tuberosum tubers have been consumed cooked as a folk remedy for the treatment of skin, lungs, liver and kidneys diseases, these uses have very limited scientific basis. Therefore, this article develops a phytochemical analysis of the yellow tubers of T. tuberosum with the objective to assess whether the isolated compounds have anti-inflammatory potential in the CCD-1109Sk, MRC-5 and RWPE-1 cell lines. We performed an extraction of T. tuberosum tubers using different organic solvents, followed by a bioguided chromatographic separation. Four macamides were identified by LC/MS techniques, but only N-benzyllinoleamide (1) and N-benzyloleamide (2) were isolated and elucidated by NMR/MS techniques, given that they were present in a larger proportion in the tubers. The anti-inflammatory potential of macamides was evaluated by the inhibition of NF-κB and STAT3 activation. Both compounds displayed inhibition of NF-κB activation with IC50 values of 2.28±0.54 µM; 3.66±0.34 µM and 4.48±0.29 µM for compound (1) and 6.50±0.75 µM; 7.74±0.19 µM and 8.37 ±0.09 µM for compound (2) in CCD-1109Sk, MRC-5 and RWPE-1 cell lines, respectively. Moreover, both compounds inhibited the STAT3 activation with IC50 of 0.61±0.76 µM; 1.24±0.05 µM and 2.10±0.12 µM for compound (1) and 5.49±0.31 µM; 7.73 ±0.94 µM and 7.79±0.30 µM for compound (2). Therefore, isolated macamides of T. tuberosum tubers showed promising anti-inflammatory effects, suggesting a possible beneficial use to combat inflammatory processes of skin, lung and prostate.

Two unknown 1,2,4-oxadiazoles (3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) and one known 1,2,4-oxadiazole (5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) were isolated from tubers of Neowerdermannia vorwerkii, collected from the San Juan Huancollo, Ingavi province, La Paz, Bolivia. The chemical structures of these compounds were elucidated through NMR and HRMS spectroscopic analyses. All compounds showed apoptotic capacity against the SK-HEP-1 and Caco-2 tumour cells. 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2, 4-oxadiazole showed slight apoptotic capacities, with an IC

Ethno-pharmacological relevance Gnaphalium polycaulon commonly known as “cudweed” has been used throughout South America as an infusion to treat colds, bronchitis, fever or pneumonia. Aim of the study This study aimed to determine the antibacterial and anti-inflammatory activities of the aqueous extract of Gnaphalium polycaulon and identify the related compounds. Materials and methods A bio-guided isolation of the active compounds of Gnaphalium polycaulon was carried out, selecting the fractions depending on their antibacterial, anti-inflammatory and cytotoxic activities. The antibacterial effect was studied against Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae; and the anti-inflammatory study was performed by measuring the inhibition of NF-κB in BEAS-2B and IMR-90 cell cultures. Results Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are 2-(4-(1-H-tetrazol-1-yl) phenyl)-2-aminopropanoic acid (1), N-phenyl-4-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine-1-carboxamide (2) and N-(4-ethoxyphenyl)-4-(2-methylimidazo-[1,2-α] pyridine-3-yl) thiazol-2-amine (3). All compounds showed antibacterial activity with MIC values of 44.80–44.85, 0.017–0.021 and 0.0077–0.0079 μM, respectively, in the Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae strains, while the positive control, Ofloxacin, had a MIC value of 27.64–27.67 μM. This was corroborated through a zone inhibition assay, where compound 3 (11.36–11.67 mm) was much more active than the positive control (Ofloxacin, 23.41–24.12 mm), while compounds 2 (26.47–27.64 mm) and 1 (28.39–29.76 mm) displayed similar antibacterial potential to the positive control. Finally, all the compounds presented NF-κB inhibitory activity, compounds 3 (IC50 = 0.0071–0.0073 μM) and 2 (IC50 = 0.016–0.019 μM) being the most promising. Compound 1 (IC50 = 44.24–44.26 μM) had less anti-inflammatory potential, being also the closest to the values displayed by the positive control (Celastrol, IC50 = 7.41 μM). Conclusion In the present study, three compounds were isolated for the first time from the aqueous extract of Gnaphalium polycaulon. Their antibacterial and anti-inflammatory potential was tested and showcased.

The tuber of Neowerdermannia vorwerkii commonly known as 'Achacana' is used as an infusion in Andean countries to treat various gastrointestinal ailments, kidney and liver diseases.This study determined the anti-inflammatory activity of the aqueous extract from Neowerdermannia vorwerkii and identified the compounds related to this activity.A bio-guided isolation of the active compounds of Neowerdermannia vorwerkii was carried out, selecting the sub-extracts and fractions depending on their anti-inflammatory activity in the Hs 738.St/Int, Hs 746T and NCI-N87 cells.Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3-(pyridin-3-yl)-5-(tiophen-3-yl)-1,2,4-oxadiazole (1), 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (2) and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (3). Regarding their anti-inflammatory activity, the three compounds inhibited the production of cytokines (IL-1β, IL-6 and TNF-α), however, compound 1 was the most active, with an ICIn the present study, the anti-inflammatory activity of the aqueous extract of Neowerdermannia vorwerkii was tested and analysed, following the isolation of three 1,2,4-oxadiazoles type compounds with similar pharmacological properties.

Activity-guided fractionations from the freshwater cyanobacterium

Three carbamidocyclophanes, A, F and V, and carbamidocylindrofridin A were isolated from the cultured freshwater cyanobacterium Cylindrospermum stagnale, collected in the Canary Islands. The chemical structures of these compounds were elucidated through NMR, HRMS and ECD spectroscopy. The absolute configuration of carbamidocyclophane A was confirmed using X-ray-diffraction. All compounds showed apoptotic capacity against the SK-MEL-1, SK-MEL-28 and SK-MEL-31 tumour cells. Carbamidocylindrofridin A had the highest anti-tumour potential, with an IC50 of 1 ± 0.3 μM in the SK-MEL-1 cell line, This work was supported by the Fundación de la Universidad Autónoma de Madrid (FUAM)

Tropaeolum tuberosum, commonly known as Mashua, is an herbal remedy used in traditional Andean medicine for the relief of kidney and bladder pain, as well as contusions. This study aimed to evaluate the fractions and isolated compounds from T. tuberosum with analgesic activity mediated by the transient receptor potential vanilloid-1 receptor. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the n-heptane fractions from samples of purple tubers of T. tuberosum. The transient receptor potential vanilloid-1 agonist and antagonist activity were assessed through the measurement of intracellular Ca2+ in HEK001 cells. The chemical structure determination led to the identification of two alkamides: N-(2-hydroxyethyl)-7Z,10Z,13Z,16Z-docosatetraenamide (1) and N-oleoyldopamine (2). Both compounds induced increased intracellular calcium flow with IC50 values of 3.2 nM and 7.9 nM, respectively, thus activating the transient receptor potential vanilloid-1 receptor. Our research is the first report to show that these two compounds isolated from T. tuberosum can act as agonists of the transient receptor potential vanilloid-1 receptor, providing scientific evidence for the traditional use of this species in pain relief.

Ethno-pharmacological relevance: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta “Huacatay” is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. Aim of the study: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. Materials and methods: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. Results: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 μg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 μM for compound 1 and 7.91–9.87 μM for compound 2. Conclusions: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort, This work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM)

Activity-guided fractionations of

Two alkaloids were isolated and identified for the first time in the black tubers of Tropaeolum tuberosum, collected from the Titicani-Taca, Ingavi province in La Paz, Bolivia. Their structures were elucidated by extensive NMR and MS spectroscopic analyses. The isolated compounds were evaluated for their cytotoxicity and apoptotic capacity against four human cancer cell lines. 2-Benzyl-3-thioxohexahydropyrrolo[1,2-c]imidazole-1-one (1) showed slight cytotoxic activity against all the cancer cell lines which were tested, with IC50 values ranging from 27.45 ± 0.80 to 31.07 ± 0.87 μM. Moreover, N-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide (2) showed significant anti-cancer potential, with IC50 values between 1.26 ± 0.57 μM and 1.37 ± 0.09 μM against all human cancer cell lines which were tested. Treatment of tumour cell lines with the compounds caused an increase in the apoptotic rate of these cells, observing that compound 2 presented an apoptotic effect which was double with respect to the control (Dimethylenastron).

One of the characteristics of cancer is that the lack of oxygen in the cancer cells triggers changes in their gene expression. This hypoxia activates hypoxia-inducible factor 1-alpha and this in turn sets in motion the whole family of important angiogenic genes for the tumour. Hypoxia-inducible factor 1-alpha therefore increases the density and vascular permeability within the tumours, facilitating their rapid growth and, later, the metastasis. Senecio graveolens is a South American medicinal plant commonly used for mountain sickness (lack of adaptation of the organism to hypoxia). Additionally, pharmacological studies showed that its alcoholic extracts have cytotoxic properties. This research aimed to perform a guided phytochemical study of S. graveolens to identify compounds capable of inhibiting hypoxia-inducible factor 1-alpha through suppression of nuclear factor kappa-light-chain-enhancer of activated B cell activation. The isolation led to the characterisation of phanurane (1), damsine (2), and scoparone (3), first reported in the S. graveolens species. Phanurane (1) showed inhibitory activity of hypoxia-inducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 = 20.66 ± 0.04 μM), A549 (IC50 =25.80 ± 0.04 μM), Hep G2 (IC50 =29.21 ± 0.03 μM), and Caco-2 (IC50 =38.58 ± 0.02 μM). Damsine (2) hypoxia-inducible factor 1-alpha displayed inhibitory activity of hypoxiainducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 =2.29 ± 0.07 μM), A549 (IC50 =4.13 ± 0.04 μM), Hep G2 (IC50 =6.40 ± 0.03 μM), and Caco-2 (IC50 =9.80 ± 0.04 μM). Finally, scoparone (3) displayed inhibitory activity of y poxiainducible factor 1-alpha on the cancer cell lines U-373 MG (IC50 =15.22±0.01μM), A549 (IC50 =17.47±0.02μM), Hep G2 (IC50=18.26±0.06μM), and Caco-2 (IC50=19.75±0.04μM). In addition, phanurane (1) displayed inhibitory activity over nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50 =7.13 ± 0.03 μM), A549 (IC50 = 8.64 ± 0.03 μM), Hep G2 (IC50 = 8.87 ± 0.04 μM), and Caco-2 (IC50 =15.11 ± 0.01 μM). Likewise, damsine (2) showed inhibitory activity over nuclear factor kappa-light-chainenhancer of activated B cells on cancer cell lines U-373 MG (IC50 =2.28 ± 0.01 μM), A549 (IC50 =3.79 ± 0.02 μM), Hep G2 (IC50 = 3.98 ± 0.05 μM), and Caco-2 (IC50 = 6.41 ± 0.02 μM). Lastly, scoparone (3) displayed inhibitory activity of nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50 = 3.62 ± 0.06 μM), A549 (IC50 = 4.48 ± 0.03 μM), Hep G2 (IC50 = 5.25 ± 0.01 μM), and Caco-2 (IC50 =11.90 ± 0.02 μM). This study corroborates the cytotoxic activity of the isolated compounds through the inhibition of hypoxia-inducible factor 1-alpha as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells, This work was supported by the National Herbarium of Bolivia, the Fundación de la Universidad Autónoma de Madrid (FUAM)

Activity-guided fractionations of black tubers of

Activity-guided fractionations of leaves and stems from

Activity-guided fractionations of black tubers of Tropaeolum tuberosum led to the isolation of 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl] benzonitrile (1) and [3,5-Bis (1,1-dimethylethyl)-4-hydroxyphenyl] ethenylidene] bis-phosphonic acid tetraethyl ester (2). Compounds 1 and 2 showed an antibacterial effect against almost all the strains assayed, especially compound 2, showing the same inhibition potential for Enterococcus faecalis and Salmonella enteritidis as the ampicillin (MIC = 1.5 μM) and a better potential than chloramphenicol which has a MIC of 3.5 μM. In addition, compounds 1 and 2 showed a relevant antifungal inhibition against Candida tropicalis with MICs of 100 μM and 50 μM, and against Saccharomyces kudriavzevii with MICs of 25 μM and 1.5 μM. This is in comparison to fluconazole which had MICs of 150 μM (against Candida tropicalis) and 3.5 μM (against Saccharomyces kudriavzevii). This is the first time that compounds 1 and 2 are reported as showing antimicrobial activities.

Activity-guided fractionations from the freshwater cyanobacterium Nodularia harveyana led to the isolation of two monogalactosyldiacylglycerols (MGDG), two digalactosyldiacylglycerols (DGDG), two monoglucosyldiacylglycerols (MGlcDG) and 1-(O-hexose)-3,25-hexacosanediol (HG). Structures were elucidated by a combination of 1D and 2D NMR analysis, HRMS and GC-MS. The potential for inhibition against TNF-α and NF-κB production of these seven compounds was tested in THP-1 cells. All compounds showed activity, but compound 7 showed higher inhibitory activity of TNF-α and NF-κB, with IC50 of 4.88 ± 0.13 and 3.64 ± 0.45 μM, respectively.

“This is an Accepted Manuscript version of the following article, accepted for publication in Natural Product Research. Natural Product Research 35.24 (2021): 5843-5847. It is deposited under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way”, Activity-guided fractionations of Jatropha macrantha Müll. Arg. led to the isolation of pomolic acid (1) and euscaphic acid (2). The potential for inhibition against NF-κB and HIF-1α production of these two compounds was tested in different tumour cell lines. Compounds 1 and 2 showed an inhibitory activity of HIF-1α in the SK-MEL-28 (IC50=3.01 ± 0.02 μM and 3.78 ± 0.02 μM), A549 (IC50=9.97 ± 0.01 μM and 10.25 ± 0.01 μM) and U-373 MG (IC50=6.34 ± 0.02 μM and 8.85 ± 0.02 μM) cell lines. In addition, compounds 1 and 2 showed an inhibitory activity on NF-κB in SK-MEL-28 (IC50=1.05 ± 0.02 μM and 2.71 ± 0.01 μM), A549 (IC50=3.63 ± 0.01 μM and 3.73 ± 0.02 μM) and U-373 MG (IC50=2.55 ± 0.02 μM and 3.39 ± 0.01 μM) cell lines. This is the first report that isolates these compounds from J. macrantha and tests their antitumor potential

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 μM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activity, This work was supported by the Fundación de la Universidad Autónoma de Madrid (FUAM)

Cybastacines A (1) and B (2) were discovered as a novel pentacyclic sesterterpenoid-alkaloid skeleton structure, with a guanidinium group. These molecules were isolated from a Nostoc sp. cyanobacterium collected in the Canary Islands. Their structures were elucidated primarily by a combination of spectroscopic analyses and X-ray diffraction. These compounds showed antibiotic activities against several clinically relevant bacterial strains.