One of the most common techniques for labeling biomolecules is by fluorescence with organic probes. Such labeling may be accomplished with fluorescent proteins or with nanocrystals.
Melanoma is the deadliest type of skin cancer, with about 61,000 deaths annually worldwide. Late diagnosis increases mortality rates due to melanoma's capacity to metastasise rapidly and patients' ...resistance to the available conventional therapies. Consequently, the interest in natural products as a strategy for drug discovery has been emerging. Propolis, a natural product produced by bees, has several biological properties, including anticancer effects. Propolis from Gerês is one of the most studied Portuguese propolis. Our group has previously demonstrated that an ethanol extract of Gerês propolis collected in 2018 (G18.EE) and its fractions (
-hexane, ethyl acetate, and
-butanol) decrease melanoma cell viability. Out of all the fractions, G18.EE-
-BuOH showed the highest potential as a melanoma pharmacological therapy. Thus, in this work, G18.EE-
-BuOH was fractioned into 17 subfractions whose effect was evaluated in A375
-mutated melanoma cells. The subfractions with the highest cytotoxic activity were analysed by UPLC-DAD-ESI/MS
in an attempt to understand which phenolic compounds could account for the anti-melanoma activity. The compounds identified are typical of the Gerês propolis, and some of them have already been linked with antitumor effectiveness. These results reaffirm that propolis compounds can be a source of new drugs and the isolation of compounds could allow its use in traditional medicine.
The demand for new fluorophores for different biological target imaging is increasing. Benzo
phenoxazine derivatives are fluorochromophores that show promising optical properties for bioimaging, ...namely fluorescent emission at the NIR of the visible region, where biological samples have minimal fluorescence emission. In this study, six new benzo
phenoxazinium chlorides possessing sulfonamide groups at 5-amino-positions were synthesized and their optical and biological properties were tested. Compared with previous probes evaluated using fluorescence microscopy, using different
strains, these probes, with sulfonamide groups, stained the vacuole membrane and/or the perinuclear membrane of the endoplasmic reticulum with great specificity, with some fluorochromophores capable of even staining the plasma membrane. Thus, the addition of a sulfonamide group to the benzo
phenoxazinium core increases their specificity and attributes for the fluorescent labeling of cell applications and fractions, highlighting them as quite valid alternatives to commercially available dyes.
A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as ...potential insecticides through the assessment of their biological activity against
insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.
Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant ...actions. New
-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line
(
), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.
Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of ...intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo
phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death.
results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.
The aim of this work was to evaluate the color stability of betalain- and anthocyanin-rich extracts in yogurt-like fermented soy, in order to develop a preliminary understanding of how these pigments ...behave in this type of food system during storage for 21 days at 4 °C. Thus, the extracts of red beetroot, opuntia, hibiscus and red radish were integrated into the yogurt-like fermented soy in two different ways-directly after lyophilization, and encapsulated in nanosystems based in soybean lecithin-as this approach has never been used to further increase the value and potential of the dairy-free alternatives of yogurt-like fermented soy. The results showed that non-encapsulated betalain-rich extracts from red radish are the most promising for coloring yogurt-like fermented soy. However, encapsulated opuntia extracts can also be an alternative to supplement the soy fermented beverages with betalains, without changing significantly the color of the system but giving all its health benefits, due to the protection of the pigments by nanoencapsulation.
ABSTRACT
Four squaraine dyes derived from 2,3,3‐trimethylindolenine and 1,1,2‐trimethyl‐1H‐benzoeindole with different combinations of barbituric groups attach to the central ring, having ester ...groups and alkyl chains in the nitrogen atoms of heterocyclic rings were synthesized. These dyes were fully characterized, and their photophysical behavior was studied in ethanol and phosphate‐buffered solution. Absorption and emission bands between 631 and 712 nm were detected, with the formation of aggregates in aqueous media, which is typical of this class of dyes. Tests carried out with 1,3‐diphenylisobenzofuran allowed us to verify the ability of the dyes to produce singlet oxygen. The interaction of synthesized dyes with human serum albumin (HSA) was also evaluated, being demonstrated a linear correlation between fluorescence intensity and protein concentration. The antifungal potential of the dyes against the yeast Saccharomyces cerevisiae was evaluated using a broth microdilution assay. In order to test the photosensitizing capacity of the synthesized dyes, tests were carried out in the dark and with irradiation, using a custom‐built light‐emitting diode that emits close to the absorption wavelength of the studied dyes. The results showed that the interaction of dyes with HSA and the antifungal activity depends on the different structural modifications of the dyes.
A series of squaraine dyes derived from 2,3,3‐trimethylindolenine and 1,1,2‐trimethyl‐1H‐benzoeindole were successfully synthesized and characterized. The possible use of the synthesized dyes as fluorescent probes for the detection of proteins was evaluated by carrying out interaction studies between the dyes and HSA. The antifungal activity of the dyes was also evaluated using Saccharomyces cerevisiae as a biological model. Taking into account the photosensitizing capacity of dyes from the squaraine family, already widely reported, tests were carried out in the dark and using irradiation with a LED systems centered at 640 and 653 nm.
New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of ...derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containing a carboxylic acid terminal. In addition, an analogue of carvacrol and thymol isomers bearing methoxyl, 1-hydroxyethyl and (3-chlorobenzoyl)oxy, instead of the three original methyl groups, was also synthesized. Several structural changes that resulted in diminished insecticide activity have been identified, but two significantly active molecules have been synthesized, one of them being less toxic to human cells than the naturally-derived starting materials. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these active molecules likely target the insect odorant binding proteins and/or acetylcholinesterase and are able to form stable complexes. For the most promising compounds, nanoencapsulation assays were carried out in liposomes of egg phosphatidylcholine/cholesterol (7 : 3) prepared by both thin film hydration and ethanolic injection methods. The compound-loaded liposomes were generally monodisperse and with sizes smaller than or around 200 nm. The thin film hydration method allowed high encapsulation efficiencies (above 85%) for both compounds and a delayed release, while for the systems prepared by ethanolic injection the encapsulation efficiency is lower than 50%, but the release is almost complete in two days.
Thymol and carvacrol derivatives were synthesised. Two of them proved to be mildly active against
Sf9
insect cell line and one has presented selectivity by proving to be less toxic to human cells than the naturally derived starting materials.
Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low‐molecular‐weight compounds from the classes of ...monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6‐hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 μM. The results evidenced that two 6‐hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC‐5) confirmed that these two derivatives possess selective anticancer activity.
Derivatives of naturally occurring phenolics were synthesized and evaluated for their cytotoxic activity toward cancer cells. Two 6‐hydroxyflavanone derivatives showed enhanced cytotoxicity against gastric adenocarcinoma and lung carcinoma cells.
![Novel Benzo[ a ]phenoxazini...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1422-0067_1661-6596/small "Novel Benzo[ a ]phenoxazinium Chlorides Functionalized with Sulfonamide Groups as NIR Fluorescent Probes for Vacuole, Endoplasmic Reticulum, and Plasma Membrane Staining")
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