The abstract discusses the development of rutin-loaded nanoliposomes and their anti-colorectal cancer activity against human carcinoma cells (HT-29). The study characterizes the nanoliposomes using the thin-film hydration method and analyzes their size, charge, and polydispersity index. The encapsulation efficiency and drug loading ability of rutin at different concentrations were investigated. The nanoliposomes were found to be stable for up to one month at 4 ºC and showed sustained drug release for up to 24 hours. The anti-cancer activity of the rutin-loaded nanoliposomes was found to be concentration-dependent and significantly improved compared to free rutin. PEGylated nanoliposomes with rutin (1.8 mg/ml) showed the highest encapsulation efficiency and drug loading ability, along with improved selectivity against cancer cells. Overall, the study provides important insights into the potential use of rutin-loaded nanoliposomes for the treatment of colorectal cancer.

Bacteria are associated with many infections that affect humans and present antibiotic resistance mechanisms, causing problems in health organisations and increased mortality rates. Therefore, it is necessary to find new antibacterial agents that can act in the treatment of these microorganisms. Geopropolis is a natural product made by stingless bees, formed by a mixture of plant resins, salivary secretions, wax and soil particles, presenting a diverse chemical composition. Thus, this study aimed to evaluate antibacterial activity, antibiotic modulation and the toxicity of geopropolis extract from the stingless bees, Melipona subnitida (Ducke, 1910) and Scaptotrigona depilis (Moure, 1942) against standard and multi-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacteria. Geopropolis samples were collected in a meliponary located in Camaragibe, Pernambuco, Brazil. To determine the Minimum Inhibitory Concentration (MIC) and antibiotic modulation we performed broth microdilution tests. Mortality tests were used to verify extract toxicity in the model Drosophila melanogaster. The microbiological tests showed that the M. subnitida extracts had better inhibitory effects compared to S. depilis, presenting direct antibacterial activity against standard and multi-resistant strains. The extracts potentialized antibiotic effects, suggesting possible synergy and did not present toxicity in the model used.

A new monoalkyl glycerol ether, 3-(n-henicosyloxy) propane-1,2-diol (1), was isolated from the CH2Cl2/MeOH crude extract of the Red Sea soft coral Nephthea mollis. Additionally, three known related analogues were identified: chimyl alcohol (2), batyl alcohol (3), and 3-(icosyloxy) propane-1,2-diol (4). The chemical structure of 3-(n-henicosyloxy) propane-1,2-diol was determined using advanced spectroscopic analyses, including 1D, 2D Nuclear Magnetic Resonance (NMR), Electron Ionization mass spectra (EI-MS), and High-Resolution Electron Spray Ionization mass spectra (HRESIMS) analyses. Furthermore, the identification of chimyl alcohol, batyl alcohol and 3-(icosyloxy) propane-1,2-diol was achieved by studying their EI mass fragmentation analyses and comparing their mass data with those previously reported in the literature. The cytotoxic activity of the Nephthea mollis crude extract and 3-(n-henicosyloxy) propane-1,2-diol was evaluated against five human cancer cell lines: HepG2 (hepatocellular carcinoma), MCF-7 (breast carcinoma), NCI-1299 (lung carcinoma), HeLa (cervical cancer cell), and HT-29 (colon adenocarcinoma). Moreover, 3-(n-henicosyloxy) propane-1,2-diol revealed moderate cytotoxicity against the HeLa cell line with an IC50 value of 24.1 μM, while showing inactivity against the remaining cell lines (IC50 >100 μM).

The composition and anticholinesterase activity of the dried MeOH extracts of Hieracium scheppigianum and H. naegelianum underground parts (rhizomes and roots), as well as the anticholinesterase activity of the dried, previously chemically characterised MeOH extracts of the flowering aerial parts of these two and 26 other Hieracium species in the strict sense (s. str.), were investigated. Furthermore, the anticholinesterase activity of 12 selected secondary metabolites of these extracts was evaluated. Using semi-preparative LC-MS, five caffeoylquinic acids and the sesquiterpene lactone crepiside E were isolated from H. scheppigianum underground parts extract. All these compounds were also identified in the underground parts extract of H. naegelianum. Quantitative LC-MS analysis showed that the analysed underground parts extracts were rich in both caffeoylquinic acids (139.77 and 156.62 mg/g of extract, respectively) and crepiside E (126.88 and 116.58 mg/g). In the Ellman method, the tested extracts showed an interesting anti-AChE and/or anti-BChE activity (IC50=0.56-1.58 mg/mL), which can be explained, at least partially, by the presence of some of their constituents. Among the metabolites tested, the best activity was revealed for the flavonoids apigenin, luteolin and diosmetin, and the sesquiterpene lactone 8-epiixerisamine A (IC50=68.09-299.37 μM).

Eleven new thiosemicarbazone derivatives (1-11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted-thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one-step easy synthesis and an eco-friendly process, the designed compounds were synthesized with yields of up to 95% from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxyl groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT–IR, 1H NMR, and 13C NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6-311++G(2d,2p) level of theory, and the experimental findings were supported. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 23.54±4.34 to 185.90±26.16 nM, 103.90±23.49 to 325.90 ±77.99 nM, and 86.15±18.58 to 287.70±43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme-ligand complex's interaction.

Sixteen triterpenoids with various skeletal types, five phenylpropanoid derivatives, and two flavonoids were isolated from a propolis sample produced by Apis mellifera collected in the Atlantic Forest of Midwest Brazil. Among these compounds, six triterpenes, namely 3β,20R-dihydroxylanost-24-en-3-yl-palmitate, (23E)-25-methoxycycloartan-23-en-3-one, 24-methylenecycloartenone, epi-lupeol, epi-a-amyrin, and epi-β-amyrin are being reported for the first time in propolis, while cycloartenone, (E)-cinnamyl benzoate, and (E)-cinnamyl cinnamate are new findings in Brazilian propolis. The presence of cycloartane- and lanostane-type triterpenoids, the latter being a class of compounds of restricted distribution in propolis worldwide, has not been reported in propolis from Midwest Brazil until now. The ethyl acetate phase obtained from the ethanol extract was effective in preventing biofilm formation by Staphylococcus aureus, with an inhibition rate of about 96% at 0.5 mg.mL-1, and with quercetin isolated as one of its active constituents. In contrast, the hexane phase exhibited notable antibacterial activity against Pseudomonas aeruginosa, inhibiting bacterial growth by 92% at 0.5 mg.mL-1; however, none of the triterpenoids isolated from this phase proved active against this pathogen. The ethanol extract was neither toxic nor mutagenic at the concentrations tested, as determined by the in vivo SMART assay on Drosophila melanogaster, even under conditions of high metabolic activation.

Abstract

This study investigates the potential of agomelatine (AGO), a synthetic melatoninergic drug, in combination with paclitaxel (PTX) for the treatment of breast cancer. The effects of AGO, PTX and melatonin (MTN) on breast cancer cell viability were investigated, focusing on the role of MT1 receptors. Cell viability and gene expression were analyzed in MCF-7 and MDA-MB-231 breast cancer cell experiments. The results show that AGO has cytotoxic effects on breast cancer cells similar to MTN. Combining AGO and MTN with PTX showed synergistic effects in MCF-7 cells. The study also reveals differences in the molecular mechanisms of breast cancer between estrogen-positive MCF-7 cells and estrogen-negative MDA-MB-231 cells. Combination with AGO and PTX affects apoptosis-associated proteins in both cell types. The findings suggest that AGO, combined with PTX, may be a promising adjuvant therapy for breast cancer and highlight the importance of MTN receptors in its mechanism of action.

From marine sponge-associated fungus Hamigera avellanea, thirteen secondary metabolies including a pair of undescribed alkaloid enantiomers (+)-hamiavemin A (4S) (+)-1 and (-)-hamiavemin A (4R) (-)-1. Compound 1 was enantiomers resolved by the Chiralpak AS-3 column, using a n-hexane/isopropanol mobile phase. Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of (+)-1 and (-)-1 were assigned tentatively by ECD calculations. Among the isolates, compound 6 showed strongest antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus,  Escherichia coli, Salmonella enterica, and Candida albicans with the MIC values of 2, 2, 16, 32, 64, and 16 μg/mL, respectively, which were stronger than that of the positive control compound, kanamycin (MIC values ranging from 4 to 128 μg/mL). In addition, compounds 1, 2, and 9 showed moderate cytotoxic activity against three cancer cell lines, HepG2, A549, and MCF-7 with the IC50 values ranging from 55.35±1.70 to 83.02±2.85 mg/mL

Since long ago, medicinal plants have played a vital role in drug discovery. Being blessed and rich in chemovars with diverse scaffolds, they have unique characteristics of evolving based on the need. The World Health Organization also mentions that medicinal plants remain at the center for meeting primary healthcare needs as the population relies on them. The plant-derived natural products have remained an attractive choice for drug development owing to their specific biological functions relevant to human health and also the high degree of potency and specificity they offer. In this context, one such esteemed phytoconstituent with inexplicable biological potential is psoralen, a furanocoumarin. Psoralen was the first constituent isolated from the plant Psoralea corylifolia, commonly known as Bauchi. Despite being a life-saver for psoriasis, vitiligo, and leukoderma, it also showed immense anticancer, anti-inflammatory, and anti-osteoporotic potential. This review brings attention to the possible application of psoralen as an attractive target for rational drug design and medicinal chemistry. It discusses the various methods for the total synthesis of psoralen, its extraction, the pharmacological spectrum of psoralen, and the derivatization done on psoralen.

This research is based on principal component analysis (PCA) and calculation of selection criteria (SC) to investigate the effect of foliar spraying of polyamine putrescine on essential oil yield, essential oil compounds, antioxidant activity, and biochemical compounds (polyphenol, flavonoid, and total phenol compounds) of Salvia officinalis. The treatments used included four levels of putrescine, Put (Control: 0, Put1: 500, Put2: 1000, and Put3: 1500 mg L− 1) with five replications. Based on our results, four factors had eigenvalues ≥ 1 and showed a cumulative variance percentage of 92.57% by applying different concentrations of putrescine. According to the results of this research, putrescine had significant effects on the amount of total phenolic compounds, flavonoids, and antioxidant activity. The crucial essential oil compounds of different Put treated sage were: cis- thujone (35.34%), Camphor (15.60%), trans- thujone (9.90%), 1,8- cineole (9.46%), α-Humulene (3.85%), α- pinene (3.50%) and limonene (1.23%). The results showed that the amount of total phenol, the phenolic composition of catechin, and the antioxidant activity of sage plant extract increased significantly when putrescine was used at 1000 mg/liter. Results can use the current research to optimize the production management of medicinal plants and improve the quality of their products.