| 1. |
- Gonzales-Ramirez, Mariela, et al.
(författare)
-
Trichilones A–E: New Limonoids from Trichilia adolfi
- 2021
-
Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:11
-
Tidskriftsartikel (refereegranskat)abstract
- In addition to the trichilianones A–D recently reported from Trichilia adolfi, a continuing investigation of the chemical constituents of the ethanol extract of the bark of this medicinal plant yielded the five new limonoids 1–5. They are characterized by having four fused rings and are new examples of prieurianin-type limonoids, having a ε-lactone which in 4 and 5 is α, β- unsaturated. The structures of the isolated metabolites were determined by high field NMR spectroscopy and HR mass spectrometry. The new metabolites were shown to have the ε-lactone fused with a tetrahydrofuran ring which is connected to an oxidized hexane ring joined with a cyclo-pentanone having a 3-furanyl substituent. As the crude extract possesses antileishmanial activity, the compounds were assayed for cytotoxic and antiparasitic activities in vitro in murine macrophage cells (raw 264.7 cells) and in Leishmania amazoniensis as well as L. braziliensis promastigotes. Metabolites 1–3 and 5 showed moderate cytotoxicity (between 30–94 μg/mL) but are not responsible for the antileishmanial effect of the extract.
|
|
| 2. |
- Haddadi, Sara, et al.
(författare)
-
Building polymer-like clusters from colloidal particles with isotropic interactions, in aqueous solution
- 2021
-
Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 581, s. 669-681
-
Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: Colloidal particles that interact via a long-ranged repulsive barrier in combination with a very short-ranged attractive minimum can “polymerize” to form highly anisotropic structures. Motivated by previous experimental achievements in non-aqueous solvents, and recent theoretical predictions, we hypothesize that it is possible to construct clusters that resemble linear or branched polymers, in aqueous solution. If these clusters are not too large, they may even remain dispersed, but even if they grow large enough to sediment, they may be collected and used in future applications.Experiments: In this work, we specifically synthesize poly (ethylene glycol) (PEG) chains, grafted onto poly(styrene) (PS) particles in aqueous solution, and adjust the conditions so that strongly anisotropic and isolated polymer-like clusters are formed. These conditions include a very low ionic strength (the particles are weakly charged), a relatively high temperature, and a low particle concentration. An important criterion is that the particle size is large enough to admit structural analyses via confocal laser scanning microscopy (CLSM). We have furthermore utilized Metropolis Monte Carlo (MC) simulation to generate theoretical predictions of these cluster formations. We have conducted such simulations of 3D as well as 2D systems, where the latter is also relevant, given that the clusters sometimes deposit onto the glass surfaces upon imaging. A simplistic particle–particle potential of mean force is adopted for the simulations, but we also invoke a more elaborate theoretical model, to demonstrate that similar interactions can be obtained when the grafted chains are treated explicitly.Findings: According to our Zeta potential measurements, the particles indeed carry a weak negative charge, presumably due to ion specific adsorption. Furthermore, by ensuring that the ionic strength is very low, with a Debye length similar to the particle size, we could use temperature to control the hydrophobicity of the grafted PEG layer, and thus the strength of the short-ranged attraction. We were indeed able to establish highly anisotropic structures, that resemble linear or branched polymers, which we could image by CLSM. The average degree of polymerization could be adjusted by a variation of the particle concentration.
|
|
| 3. |
- Ishchuk, Olena P., et al.
(författare)
-
Simple carbohydrate derivatives diminish the formation of biofilm of the pathogenic yeast candida albicans
- 2020
-
Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.
|
|
| 4. |
- Limachi, Ivan, et al.
(författare)
-
Trichilianones A-D, Novel Cyclopropane-Type Limonoids from Trichilia adolfi
- 2021
-
Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 26:4
-
Tidskriftsartikel (refereegranskat)abstract
- The fractionation of an ethanol extract of the bark of Trichilia adolfi yielded four novel limonoids (trichilinones A-D, 1-4), with five fused rings and related to the hortiolide-type limonoids. Starting with an ε-lactone, which is α,β-unsaturated in trichilinones A and D (1 and 4), attached to a tetrahydrofuran ring that is connected to an unusual bicyclo [5.1.0] hexane system, joined with a cyclopentanone with a 3-furanyl substituent [(2-oxo)-furan-(5H)-3-yl in trichilinone D (4)], the four compounds isolated display a new 7/5/3/5/5 limonoid ring system. Their structures were established based on extensive analysis of NMR spectroscopic data. As the crude extract possessed anti-leishmanial properties, the compounds were assayed for cytotoxic and anti-parasitic activities in vitro in murine macrophages cells (Raw 264.7) and leishmania promastigotes (L. amazoniensis and L. braziliensis), respectively. The compounds showed moderate cytotoxicity (approximately 70 μg/mL), but are not responsible for the leishmanicidal effect of the extract.
|
|
| 5. |
- Mastio, Roberto, et al.
(författare)
-
Fluorescently labeled xylosides offer insight into the biosynthetic pathways of glycosaminoglycans
- 2021
-
Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 11:60, s. 38283-38292
-
Tidskriftsartikel (refereegranskat)abstract
- Five novel xylosides tagged with the fluorescent probe Pacific Blue™ were synthesized and found to act as substrates for β4GalT7, a bottleneck enzyme in the biosynthetic pathways leading to glycosaminoglycans. By confocal microscopy of A549 cells, we showed that the xylosides were taken up by the cells, but did not enter the Golgi apparatus where most of the glycosaminoglycan biosynthesis occurs. Instead, after a possible double galactosylation by β4GalT7 and β3GalT6, the biosynthesis was terminated. We hypothesize this is due to the charge of the fluorescent probe, which is required for fluorescent ability and stability under physiological conditions.
|
|
| 6. |
- Terrazas, Paola, et al.
(författare)
-
SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality
- 2020
-
Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 25:13
-
Tidskriftsartikel (refereegranskat)abstract
- Pulchrol (1) is a natural benzochromene isolated from the roots of Bourreria pulchra, shown to possess potent antiparasitic activity towards both Leishmania and Trypanozoma species. As it is not understood which molecular features of 1 are important for the antiparasitic activity, several analogues were synthesized and assayed. The ultimate goal is to understand the structure-activity relationships (SAR:s) and create a QSAR model that can be used for the development of clinically useful antiparasitic agents. In this study, we have synthesized 25 2-methoxy-6,6-dimethyl-6H-benzo[c]chromen analogues of 1 and its co-metabolite pulchral (5a), by semi-synthetic procedures starting from the natural product pulchrol (1) itself. All 27 compounds, including the two natural products 1 and 5a, were subsequently assayed in vitro for antiparasitic activity against Trypanozoma cruzi, Leishmania brasiliensis and Leishmania amazoniensis. In addition, the cytotoxicity in RAW cells was assayed, and a selectivity index (SI) for each compound and each parasite was calculated. Several compounds are more potent or equi-potent compared with the positive controls Benznidazole (Trypanozoma) and Miltefosine (Leishmania). The compounds with the highest potencies as well as SI-values are esters of 1 with various carboxylic acids.
|
|
| 7. |
- Terrazas, Paola, et al.
(författare)
-
SARs for the antiparasitic plant metabolite pulchrol. : 3. Combinations of new substituents in A/B-rings and A/C-rings
- 2021
-
Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:13
-
Tidskriftsartikel (refereegranskat)abstract
- The natural products pulchrol and pulchral, isolated from the roots of the Mexican plant Bourreria pulchra, have previously been shown to possess an antiparasitic activity toward Trypanosoma cruzi, Leishmania braziliensis and L. amazonensis, protozoa responsible for the Chagas disease and leishmaniasis. These infections have been classified as neglected diseases, and still require the development of safer and more efficient alternatives to their current treatments. Recent SAR stud-ies, based on the pulchrol scaffold, showed which effect the exchanges of its substituents have on the antileishmanial and antitrypanosomal activity. Many of the analogues prepared were shown to be more potent in vitro than pulchrol and the current drugs used to treat Leishmaniasis and the Chagas disease (Miltefosine and Benznidazole respectively). Moreover, indications of some of the possible interactions that may take place in the binding sites were also identified. In this study, 12 analogues with modifications at two or three different positions in two of the three rings were prepared by synthetic and semi-synthetic procedures. The molecules were assayed in vitro to-ward T. cruzi epimastigotes, L. braziliensis promastigotes and L. amazonensis promastigotes. Some compounds had higher antiparasitic activity than the parent compound pulchrol, and in some cases even Benznidazole and Miltefosine. The best combinations in this subset are with carbonyl functionalities in the A-ring and isopropyl groups in the C-ring, as well as with alkyl substituents in both the A- and C-rings combined with a hydroxyl group in position 1 (C-ring). The latter corresponds to cannabinol, which was shown to be potent toward all parasites.
|
|
| 8. |
- Willén, Daniel, et al.
(författare)
-
Azide-Functionalized Naphthoxyloside as a Tool for Glycosaminoglycan Investigations
- 2021
-
Ingår i: Bioconjugate Chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 32:12, s. 2507-2515
-
Tidskriftsartikel (refereegranskat)abstract
- We present a xylosylated naphthoxyloside carrying a terminal azide functionality that can be used for conjugation using click chemistry. We show that this naphthoxyloside serves as a substrate for β4GalT7 and induces the formation of soluble glycosaminoglycan (GAG) chains with physiologically relevant lengths and sulfation patterns. Finally, we demonstrate its usefulness by conjugation to the Alexa Fluor 647 and TAMRA fluorophores and coupling to a surface plasmon resonance chip for interaction studies with the hepatocyte growth factor known to interact with the GAG heparan sulfate.
|
|
