Search Results (24)

We synthesized 16 representatives of a new class of tetraene macrodiolides with two pharmacophore cis,cis-1,5-diene fragments of the molecule in their structure in rather high yields (from 67 to 84%), which, in turn, were synthesized by a catalytic intermolecular cyclocondensation reaction of α,ω-alka-nZ,(n+4)Z-diendiols with α,ω-alka-nZ,(n+4)Z-diendioic acids using Hf(OTf)₄. The synthesis of starting substrates with 1Z,5Z-diene moieties with a high degree of stereoselectivity was carried out using the authors’ original reaction of catalytic homo-cyclomagnesiation of O-containing allenes. The cytotoxic potential of the examined compounds was assessed using the following cell lines: Jurkat, K562, U937, HL60, HEK293, and Wi-38 (fibroblasts). Biological tests of the synthesized compounds showed a direct effect on mitochondrial biogenesis by the dissociation of oxidation and phosphorylation and the release of cytochrome P450 into the cell cytosol, as well as the induction of mitochondrial apoptosis. The selectivity index demonstrates significant variability, ranging from approximately 2.5 to 5.3 for Jurkat cells and from 3.0 to 5.8 for the other cell lines. Full article

In Thailand, wild yam, or Dioscorea hispida Dennst., is a starchy crop that is usually underutilized in industry. The purpose of this study was to isolate the starch and extract the phytochemical from D. hispida and use them in cosmetics. Starch was used instead of talcum, which can cause pulmonary talcosis in dusting powder formulas (DP 1-5). GC-MS was used to identify the bioactive components present in the ethanolic extract of D. hispida. The main compounds were identified as 9,12-octadecadienoic acid (Z,Z)- (6.51%), stigmasta-5,22-dien-3-ol, (3.beta.,22E)- (6.41%), linoleic acid ethyl ester (5.72%), (Z,Z)-9,12-octadeca-dienoic acid, 2,3-dihydroxy-propyl (3.89%), and campesterol (3.40%). Then, the extract was used as an ingredient in facial sleeping mask gel formulas (SM 1–SM 5). Stability tests, physical characteristics, enzyme inhibitions, and sensitization dermal toxicity tests were used to evaluate the DP and SM formulations. The results showed that the fresh tubers of D. hispida showed a 12.5% w/w starch content. The findings demonstrated that starch powder had a restricted size distribution, ranging from 2 to 4 μm, and a smooth surface that was polygonal. Following stability testing, the color, odor, size, and flowability of all DP formulations did not significantly differ. The SEM investigation revealed that DP particles were homogenous. For the sensitization dermal toxicity test, DP denoted no erythema or skin irritation in the guinea pigs. After stability testing, the colors of the SM formulas were deeper, and their viscosity slightly increased. The pH did not significantly change. After the stability test, SM formulas that contained Glycyrrhiza glabra and D. hispida extracts exhibited stable tyrosinase and elastase inhibitory activities, respectively. In the sensitization dermal toxicity test, guinea pigs showed skin irritation at level 2 (not severe) from SM, indicating that redness developed. All of these findings indicate that D. hispida is a plant that has potential for use in the cosmetics industry. Furthermore, D. hispida starch can be made into a beauty dusting powder, and more research should be conducted to develop an effective remedy for patients or those with skin problems. Full article

Macrocyclic compounds, including macrolactones and macrodiolides, play a significant role in the development of supramolecular chemistry, materials science, the perfume industry, and pharmaceuticals. In previous studies conducted by our group over several years, previously undescribed macrocyclic compounds containing pharmacophoric 1Z,5Z- diene fragments in their structure were synthesized for the first time, which showed high potential in studies on cytotoxicity, apoptosis-inducing activity, effects on the cell cycle, and mitochondria in tumor cell lines (Jurkat, K562, U937). As part of the continuing research on the development of methods for synthesizing new unsaturated macrodiolides and studying their antitumor properties, this work presents, for the first time, the stereoselective synthesis of macrocyclic compounds based on 1,14 -tetradeca-5Z,9Z-dienoic acid and α,ω-alka-nZ, (n + 4)Z-dienediols (1,12-dodeca-4Z,8Z-dienediol, 1,14-tetradeca-5Z,9Z-dienediol, 1,16-octadeca-6Z,10Z-dienediol) in good yields. The method for the synthesis of new macrodiolides is based on the previously well-proven reaction of direct intermolecular cyclocondensation of dienedioic acid with diene diols in the presence of 5 mol.% hafnium(IV) triflate. As a result of the experiments, it was shown that the reaction between 1,14-tetradeca-5Z,9Z-dienedioic acid and 1,16-octadeca-6Z,10Z-dienediol in toluene proceeded within 18 h with the highest yield of 76%, with the formation of previously undescribed tetraenoic macrodiolides containing two 1Z,5Z-diene fragments in their structure. Full article

Macrocycles represent an important class of compounds that are widespread in nature. Of particular interest to researchers are aromatic macrocyclic compounds, which, due to their rigid structure and unique physicochemical properties, can find application in many areas of science, industry and medicine. Previously, we synthesized polyether aromatic macrodiolides, which showed intriguing antitumor properties. In the work, Peyrottes S. and co-authors showed that the introduction of biphenyl or naphthyl rings, as well as triple bonds, into the structure of the compounds they synthesized, not only helps to reduce the molecular flexibility of the molecule, but also increases the bioavailability after oral administration of the corresponding neutral prodrugs. Studies in mice have shown that the presence of two aromatic groups is well tolerated and has resulted in compounds with valuable properties in vitro and in vivo. Based on these results, in continuation of our research on the synthesis of biologically active macrodiolides, in the framework of this work, new aromatic macrocycles were synthesized, the structure of which, along with the 1Z,5Z-diene fragment, contains phenyl or naphthyl rings. The target polyester macrodiolides were obtained by Hf-catalyzed intermolecular cyclocondensation of 1,14-tetradeca-5Z,9Z-dienedioic acid with diols synthesized from dihydroxybenzenes and naphthalenediols. Full article

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1β, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders. Full article

For the first time, a synthetic analogue of natural (5Z,9Z)-dienoic acid has been synthesized in the form of a hybrid molecule containing a fragment of oleanolic acid and (5Z,9Z)-tetradeca-5.9-dienedicarboxylic acid, synthesized using a new reaction of Ti-catalyzed homo-cyclomagnesiation 1,2-dienes. The high cytotoxic activity of (5Z,9Z)-14-[(3,28-dioxoolean-12-en-28-yl)oxy]tetradeca-5,9-dienoic acid against tumor cells Jurkat, K562, U937 and HL60 was established. This compound is also an inducer of apoptosis, affects the cell cycle and inhibits human topoisomerase I. Full article

Stereoselective synthesis of (7Z,11Z)-octadeca-7,11-diene-1,18-dioic acid was carried out using a homo-cyclomagnesiation reaction of 2-(nona-7,8-dien-1-yloxy)tetrahydro-2H-pyran. After Steglisch esterification of the synthesized acid and polyester acetylenes in the presence of DCC and DMAP, the corresponding diesters were synthesized in good yields (67–75%). Based on symmetric diesters with terminal triple bonds, polyether macrodiolides containing conjugated triple bonds and pharmacophoric cis,cis-1,5-diene fragments in their structure were synthesized for the first time. Full article

Based on (5Z,9Z)-tetradeca-5,9-diene-1,14-dioic acid, previously undescribed polyether aromatic macrodiolides were synthesized in good yields (53–67%). The cytotoxicity of the resulting macrocyclic compounds in vitro against tumor Jurkat cells, K562 cells, conditionally normal Hek293 cell lines and normal fibroblasts was the assessment carried out. The ability of the most active macrodiolide to induce apoptosis toward Jurkat cells and influence the cell cycle was studied. Full article

Vouacapoua americana (Fabaceae) is an economically important tree in the Amazon region and used for its highly resistant heartwood as well as for medicinal purposes. Despite its frequent use, phytochemical investigations have been limited and rather focused on ecological properties than on its pharmacological potential. In this study, we investigated the phytochemistry and bioactivity of V. americana stem bark extract and its constituents to identify eventual lead structures for further drug development. Applying hydrodistillation and subsequent GC-MS analysis, we investigated the composition of the essential oil and identified the 15 most abundant components. Moreover, the diterpenoids deacetylchagresnone (1), cassa-13(14),15-dien-oic acid (2), isoneocaesalpin H (3), (+)-vouacapenic acid (4), and (+)-methyl vouacapenate (5) were isolated from the stem bark, with compounds 2 and 4 showing pronounced effects on Methicillin-resistant Staphylococcus aureus and Enterococcus faecium, respectively. During the structure elucidation of deacetylchagresnone (1), which was isolated from a natural source for the first time, we detected inconsistencies regarding the configuration of the cyclopropane ring. Thus, the structure was revised for both deacetylchagresnone (1) and the previously isolated chagresnone. Following our works on Copaifera reticulata and Vatairea guianensis, the results of this study further contribute to the knowledge of Amazonian medicinal plants. Full article

Efficient methods for the synthesis of previously undescribed hybrid compounds based on monocarbonyl derivatives of curcumin and 5Z,9Z-dienoic acid with yields of 58–66% are presented. The key monomer, (5Z,9Z)-icosa-5,9-dienoic acid, was prepared using the stereoselective cross-cyclomagnesiation reaction of aliphatic and oxygen-containing 1,2-dienes catalyzed by Cp₂TiCl₂. Full article

A significant area of study and upgrading for increasing sensitivity and general performances of matrix-assisted laser-desorption ionization (MALDI) mass spectrometry (MS) is related to matrix design. Several efforts have been made to address the challenge of low-mass-region interference-free for metabolomics analysis and specifically for lipidomics. To this aim, rationally designed matrices as 4-chloro-α-cyanocinnamic acid (ClCCA) were introduced and reported to provide enhanced analytical performances. We have taken this rational design one step further by developing and optimizing new MALDI matrices with a range of modifications on the CHCA core, involving different functionalities and substituents. Of particular interest was the understanding of the electron-withdrawing (e.g., nitro-) or donating (e.g., methoxy-) effects along with the extent of conjugation on the ionization efficiency. In the present work, ten matrices were designed on a reasonable basis, synthesized, and characterized by NMR and UV spectroscopies and laser desorption ionization. With the assistance of these putative MALDI matrices, samples containing phospholipids (PL), and neutral di-/tri-acylglycerols (DAG, TAG) were investigated using milk, fish, blood, and human plasma extracts. In comparison with CHCA and ClCCA, four of them, viz. [(2E,4E)-2-cyano-5-(4-methoxyphenyl)penta-2,4-dienoic acid] (1), [(2E,4E)-2-cyano-5-(4-nitrophenyl)penta-2,4-dienoic acid] (2), [(E)-2-cyano-3-(6-methoxynaphthalen-2-yl)acrylic acid] (6) and [(E)-2-cyano-3-(naphthalen-2-yl)acrylic acid] (7) displayed good to even excellent performances as MALDI matrices in terms of ionization capability, interference-free spectra, S/N ratio, and reproducibility. Especially compound 7 (cyano naphthyl acrylic acid, CNAA) was the election matrix for PL analysis and matrix 2 (cyano nitrophenyl dienoic acid, CNDA) for neutral lipids such as DAG and TAG in positive ion mode. Full article

Glasswort (Salicornia herbacea L.) is a halophyte that exhibits antioxidant and antidiabetic effects. Only a few studies have been conducted on its antioxidant effects. Here, we isolated an antioxidant using an activity-based purification method, and the resulting compound was identified as (9Z,11E)-13-Oxooctadeca-9,11-dienoic acid (13-KODE). We investigated its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide-stimulated RAW 264.7 macrophage cells. We studied the anti-inflammatory effects of 13-KODE derived from S. herbacea L on RAW 264.7 macrophages. 13-KODE inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production by suppressing inducible NO synthase and suppressed LPS-induced tumor necrosis factor and interleukin-1β expression in RAW 264.7 macrophages. LPS-mediated nuclear localization of NF-κB and mitogen-activated protein kinase activation were inhibited by 13-KODE. 13-KODE significantly reduced LPS-induced production of reactive oxygen species and increased the expression of nuclear factor erythroid-2 like 2 (Nfe2I2) and heme oxygenase 1. Overall, our results indicate that 13-KODE may have potential for treating inflammation. Full article

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg⁻¹ of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg⁻¹ of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg⁻¹ of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC₅₀) = 4.23 ± 0.18 µg mL⁻¹ of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL⁻¹ of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations. Full article

The synthesis of previously undescribed aromatic polyether macrodiolides containing a 1Z,5Z-diene moiety was carried out in 56–72% yields and with >98% stereoselectivity. It has been shown that the synthesized macrodiolides exhibit higher cytotoxic activity in vitro against a number of tumor cell lines (Jurkat, K562 and U937). Full article