Search Results (20)

Lacticaseibacillus species have shown potential in managing hyperglycemia, hypercholesterolemia, and oxidative stress, depending on the strain and species. This study aimed to isolate a novel Lacticaseibacillus rhamnosus strain from healthy newborns and assess its hypoglycemic and antioxidative activity, along with other probiotic properties. A non-hemolytic L. rhamnosus LBUX2302 was isolated, and it exhibited survival rates of 2.7%, 22%, and 27.5% at pH 2, 3, and 5 for 120 min. It metabolized various carbon sources and showed resistance to gentamicin, dicloxacillin, and penicillin; coaggregated with Salmonella typhi ATCC14028, Staphylococcus aureus STCC6538, and Escherichia coli O157:H7. L. rhamnosus LBUX2302 showed hydrophobicity, autoaggregation, and adhesion to HaCat, HeLa, MCF-7, SK-LU-1, and SW620 cell lines. It also exhibited extracellular activity of bile salt hydrolase. Enzymatic inhibition assays revealed 66% and 24% inhibitions of α-amylase and α-glucosidase, respectively. Its cell-free supernatant inhibited DPPH (89%), hydroxyl (81%), and superoxide anion radicals (61%). Also, antioxidant activity was observed in whole cells and cell fragments. Finally, the presence of ferulic acid activity was detected. The results highlight L. rhamnosus LBUX2302 as a promising probiotic with hypoglycemic and antioxidant effects, warranting further in vivo evaluation for its possible inclusion in functional food and health formulations. Full article

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and β-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC₅₀ value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC₅₀ value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC₅₀ value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions. Full article

From the aerial parts of Salvia carranzae Zamudio and Bedolla, three new icetexane-type diterpenoids were isolated. Their structures were established through spectroscopic methods and named the following: salvicarranzanolide (1), 19-deoxo-salvicarranzanolide (2) and 19-deoxo-20-deoxy-salvicarranzanolide (3). In addition, the known icetexane-type diterpenoids, 6,7,11,14-tetrahydro-7-oxo-icetexone (4), iso-icetexone (5), 19-deoxo-iso-icetexone (6), icetexone (7), 19-deoxo-icetexone (8) and 7α-acetoxy-6,7-dihydroicetexone (9), were also isolated, along with the abietanes sessein (10) and ferruginol (11). α-Tocopherol was also identified. Compounds 5, 6 and 8 were tested for their antiproliferative activity using the sulforhodamine B assay on six cancer and one normal human cell lines. Diterpenoids 5 and 6 showed noteworthy antiproliferative activity, exhibiting an IC₅₀ (μM) = 0.43 ± 0.01 and 1.34 ± 0.04, respectively, for U251 (glioblastoma), an IC₅₀ (μM) = 0.45 ± 0.01 and 1.29 ± 0.06 for K5621 (myelogenous leukemia), 0.84 ± 0.07 and 1.03 ± 0.10 for HCT-15 (colon cancer), and 0.73 ± 0.06 and 0.95 ± 0.09 for SKLU-1 (lung adenocarcinoma) cell lines. On the other hand, the phytotoxicity of compounds 5–7 and 9–10 was evaluated on seed germination and root growth in some weeds such as Medicago sativa, Panicum miliaceum, Amaranthus hypochondriacus and Trifolium pratense as models. While compounds 5 and 10 exhibited a moderate inhibitory effect on the root growth of A. hypochondriacus and T. pratense at 100 ppm, the diterpenoids 6, 7 and 9 were ineffective in all the plant models. Taxonomic positions based on the chemical profiles found are also discussed. Full article

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four β-cyclodextrin (βCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d₆ and the self-inclusion process was studied in D₂O by ¹H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the βCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-βCD platforms and the classical PAMAM-βCD dendrimer. Finally, we determined the toxicity for all EDTA-βCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-βCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery. Full article

Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC₅₀ of CSE for the 2D model was 80.28 μg/mL versus 530 μg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE’s primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included. Full article

Auranofin, as a thioredoxin reductase (TrxR) inhibitor, has promising anti-cancer activity in several cancer types. However, little is known about the inhibitory effect of auranofin on lung cancer cell growth. We, therefore, investigated the antigrowth effects of auranofin in various lung cancer cells with respect to cell death, reactive oxygen species (ROS), and glutathione (GSH) levels. Treatment with 0~5 µM auranofin decreased cell proliferation and induced cell death in Calu-6, A549, SK-LU-1, NCI-H460, and NCI-H1299 lung cancer cells at 24 h. In addition, 0~5 µM auranofin increased ROS levels, including O₂^•−, and depleted GSH levels in these cells. N-acetyl cysteine (NAC) prevented growth inhibition and mitochondrial membrane potential (MMP, ∆Ψm) loss in 3 and 5 µM auranofin-treated Calu-6 and A549 cells at 24 h, respectively, and decreased ROS levels and GSH depletion in these cells. In contrast, L-buthionine sulfoximine (BSO) enhanced cell death, MMP (∆Ψm) loss, ROS levels, and GSH depletion in auranofin-treated Calu-6 and A549 cells. Treatment with 3 and 5 µM auranofin induced caspase-3 activation and poly (ADP ribose) polymerase (PARP) cleavage in Calu-6 and A549 cells, respectively. Both were prevented by NAC, but enhanced by BSO. Moreover, TrxR activity was reduced in auranofin-treated Calu-6 and A549 cells. That activity was decreased by BSO, but increased by NAC. In conclusion, these findings demonstrate that auranofin-induced cell death is closely related to oxidative stress resulted from increased ROS levels and GSH depletion in lung cancer cells. Full article

Casiopeinas are a family of copper(II) coordination compounds that have shown an important antineoplastic effect and low toxicity in normal cells. These compounds induce death cells by apoptosis through a catalytic redox process with endogenous reducing agents. Further studies included a structural variation, improving the activity and selectivity in cancer cells or other targets. In the present work we report the third generation, which contains a bioactive monocharged secondary ligand, as well as the design, synthesis, characterization and antiproliferative activity, of sixteen new copper(II) coordination compounds with curcumin or dimethoxycurcumin as secondary ligands. All compounds were characterized by elemental analysis, FTIR, UV-Vis, magnetic susceptibility, mass spectra with MALDI-flight time, cyclic voltammetry, electron paramagnetic resonance (EPR) spectroscopy and X-ray diffraction. Crystallization of two complexes was achieved in dimethylsulfoxide (DMSO) with polar solvent, and crystal data demonstrated that a square-based or square-base pyramid geometry are possible. A 1:1:1 stoichiometry (diimine: copper: curcuminoid) ratio and the possibility of a nitrate ion as a counterion were supported. ¹H, ¹³C NMR spectra were used for the ligands. A sulforhodamine B assay was used to evaluate the cytotoxicity effect against two human cancer cell lines, SKLU-1 and HeLa. Electronic descriptors and redox potential were obtained by DFT calculations. Structure–activity relationships are strongly determined by the redox potential (E_1/2) of copper(II) and molar volume (V) of the complexes. These compounds can be used as a template to open a wide field of research both experimentally and theoretically. Full article

Chromenes are compounds that may be useful for inhibiting topoisomerase and cytochrome, enzymes involved in the growth of cancer and fungal cells, respectively. The aim of this study was to synthesize a series of some novel 2-amino-3-cyano-4-aryl-6,7-methylendioxy-4H-chromenes 4a–o and 2-amino-3-cyano-5,7-dimethoxy-4-aryl-4H-chromenes 6a–h by a three-component reaction, and test these derivatives for anticancer and antifungal activity. Compounds 4a and 4b were more active than cisplatin (9) and topotecan (7) in SK-LU-1 cells, and more active than 9 in PC-3 cells. An evaluation was also made of the series of compounds 4 and 6 as potential antifungal agents against six Candida strains, finding their MIC₅₀ to be less than or equal to that of fluconazole (8). Molecular docking studies are herein reported, for the interaction of 4 and 6 with topoisomerase IB and the active site of CYP51 of Candida spp. Compounds 4a–o and 6a–h interacted in a similar way as 7 with key amino acids of the active site of topoisomerase IB and showed better binding energy than 8 at the active site of CYP51. Hence, 4a–o and 6a–h are good candidates for further research, having demonstrated their dual inhibition of enzymes that participate in the growth of cancer and fungal cells. Full article

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC₅₀ of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5. Full article

Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC^® 25923, L. monocytogenes ATCC^® 19115) and two Gram-negative strains (E. coli ATCC^® 25922, P. aeruginosa ATCC^® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study. Full article

Benthic dinoflagellates produce a wide array of bioactive compounds, primarily polyketides, that cause toxic effects on human consumers of seafood and perhaps mediate species interactions in the benthic microenvironment. This study assesses toxic and other bioactive effects of the benthic dinoflagellate Amphidinium operculatum (strain AA60) in two targeted bioassays. The brine shrimp (Artemia salina) bioassay revealed lethal effects of direct exposure to live dinoflagellate cells (Treatment A) and even higher potency with ethanolic extracts of lysed cells (Treatment D). There were no inimical bioactive effects of components released to the aqueous growth medium (Treatment B) or from aqueous cell lysates (Treatment C). The hypothesis that released bioactive compounds provide a chemical defense against metazoan grazers is therefore not supported by these results. The cytotoxic effect of ethanolic crude extracts of this dinoflagellate exhibited mild to high growth reduction effects on six human cancer cell lines. In particular, crude cell-free extracts proved highly growth-inhibitory activity towards breast and lung cancer cell lines MCF-7 and SKLU-1, respectively. Preliminary anti-cancer results indicate that natural bioactive compounds from Amphidinium are worthy of structural characterization and further toxicological investigation as potential therapeutants. Full article

Decades of research has convinced us that phytochemical compounds contained within the plant products are the real deal, and they provide benefits such as health maintenance an d cure to illnesses. One of the deadliest noncommunicable diseases today is lung cancer, hence its disease management still deserves attention. Wnt/β-catenin pathway activation conferring cancer stem cell (CSC) activities to non-small cell lung carcinomas (NSCLCs) may explain why the disease is still difficult to cure. In the present study, we assessed several representatives of phytochemical categories consisting of alkaloids, chalcones and isothiocyanates for their inhibitory activity to nuclear localization of β-catenin—an important event for Wnt/β-catenin pathway activation, in lung cancer cell lines. Real-time cell analyzer confirmed that evodiamine (EVO), chelidonine (CHE), isoliquiritigenin (ISO), licochalcone-A (LICO), benzyl isothiocyanate (BI) and phenethylisothiocyanate (PI) exhibited anti-proliferative activities and cytotoxicities to adenocarcinoma cell line SK-LU-1 and human lung CSC primary cell line (HLCSC). Immunofluorescence assay identified that CHE, ISO, LICO, BI and PI were capable of reducing the number of cells harboring β-catenin within the nuclei of these cells. We extended the characterizations of BI and PI in Wnt-dependent squamous cell carcinoma cell line NCI-H1703 on several CSC functions and found that BI was better at inhibiting soft agar colony formation as an output of self-renewal ability, whereas PI was more effective in inhibiting the growth of multicellular tumor spheroid model mimicking micrometastases. Both however were not able to inhibit migration and invasion of NCI-H1703. In conclusion, BI could potentially be used as a safer alternative to target undifferentiated CSCs as adjuvant therapy, whereas PI could be used as chemotherapy to remove bulk tumor. Full article

Seven compounds, carbazole alkaloids (heptaphylline, 7-methoxyheptaphylline, 7-methoxymukonal) and coumarins (clausarin, dentatin, nordentatin, and xanthoxyletin), were isolated from the root bark of Clausena harmandiana. Antioxidation, cytotoxicity and apoptosis induction were evaluated in vitro. Results showed that clausarin exerted the highest DPPH radical scavenging and 7-methoxymukonal had the highest ferric reducing antioxidant power. In contrary, dentatin was the least DPPH radical scavenger, and heptaphylline was the least reducing antioxidant power. The isolated compounds showed different cytotoxicity. The hepatocellular carcinoma (HepG2) was generally more sensitive to the isolated compounds than lung cancer (SK-LU-1), colon cancer (HCT-116), and noncancerous (Vero) cell lines, respectively. Clausarin possessed the highest cytotoxicity selectively against cancer cell lines tested. 7-Methoxymukonal and 7-methoxyheptaphylline exhibited less cytotoxicity only in HepG2 cells and were inactive in the SK-LU-1 and HCT116 cells. Despite xantoxyletin possessing low antioxidant and low cytotoxic activity, it induced the highest apoptosis percentage with the lowest necrosis percentage of HepG2 cells after 24 h. In conclusion, xantoxyletin primarily show potential anticancer activity. The root bark of C. harmandiana is a good source of bioactive compounds or the lead for the development of new pharmaceutical agent. Full article

Dipterocarpus alatus (Dipterocarpaceae) is a medicinal plant whose use is well known for the treatment of genito-urinary diseases. However, there is no report of its cytotoxic potential. In this study, the chemical composition, antioxidant and cytotoxic activities of extracts of the leaves, bark, twigs and oleo-resin from D. alatus are investigated. Cytotoxicity was measured by the neutral red (NR) assay against HCT116, SKLU1, SK-MEL2, SiHa and U937 cancer cell lines and antioxidant capacity was evaluated by DPPH, ABTS radical scavenging, and ferric reducing antioxidant power (FRAP) assays. The chemical composition was analyzed by gas chromatography–mass spectrometry (GC-MS). Leaf, bark and twig extracts exhibited stronger antioxidant activity than oleo-resin, with bark extract showing the highest antioxidant activity and the highest total phenolic content. All samples showed more cytotoxic activity against the U937 cell line than HCT116, SKLU1, SK-MEL2 and SiHa cells with oleo-resin being more cytotoxic than melphalan against U937 cells. Chemical composition analysis of oleo-resin by GC-MS showed that the major components were sesquiterpenes, namely α-gurjunene (30.31%), (-)-isoledene (13.69%), alloaromadendrene (3.28%), β-caryophyllene (3.14%), γ-gurjunene (3.14%) and spathulenol (1.11%). The cytotoxic activity of oleo-resin can be attributed to the sesquiterpene content, whereas the cytotoxic and antioxidant activities of leaf, bark and twig extracts correlated to total phenolic content. Full article

At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the β-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the β-diketone function, while the ¹H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC₅₀ = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 μM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)₂Mg), or ca. 2-fold higher ((DAC)₂Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds. Full article