Development,Characterization, and Immunomodulatory Evaluation of Carvacrol-loaded Nanoemulsion

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% w/w oily phase (medium chain triglycerides + CV), 2% w/w surfactants (Tween 80^®/Span 80^®), and 93% w/w water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of −10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.     

Chlovalicin B,a Chlorinated Sesquiterpene Isolated from the Marine Mushroom Digitatispora marina

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM.     

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells

Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether Miodesin^TM (10 µg/mL = IC₈₀; 200 µg/mL = IC₅₀), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 10⁷ to 5 × 10⁷/mL) and LPS (1 μg/mL), respectively. Miodesin^TM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C–C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of Miodesin^TM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 Miodesin^TM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1β, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, Miodesin^TM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that Miodesin^TM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.     

Chemical Composition and Antifungal Activity of Myrcia multiflora and Eugenia florida Essential Oils

The essential oils of three specimens of Myrcia multiflora (A, B and C) and Eugenia florida were extracted by hydrodistillation, and the chemical compositions from the essential oils were identified by gas chromatography and flame ionization detection (CG/MS and CG-FID). The fungicide potential of the EOs against five fungicide yeasts was assessed: Candida albicans INCQS-40175, C. tropicalis ATCC 6258, C. famata ATCC 62894, C. krusei ATCC 13803 and C. auris IEC-01. The essential oil of the specimen Myrcia multiflora (A) was characterized by the major compounds: α-bulnesene (26.79%), pogostol (21.27%) and δ-amorphene (6.76%). The essential oil of the specimen M. multiflora (B) was rich in (E)-nerolidol (44.4%), (E)-γ-bisabolene (10.64%) and (E,E)-α-farnesene (8.19%), while (E)-nerolidol (92.21%) was the majority of the specimen M. multiflora (C). The sesquiterpenes seline-3,11-dien-6-α-ol (12.93%), eremoligenol (11%) and γ-elemene (10.70%) characterized the chemical profile of the EOs of E. florida. The fungal species were sensitive to the essential oil of M. multiflora (B) (9–11 mm), and the lowest inhibitory concentration (0.07%) was observed in the essential oil of M. multiflora (A) against the yeasts of C. famata. Fungicidal action was observed in the essential oils of M. multiflora (A) against C. famata, with an MIC of 0.78 µL/mL and 3.12 µL/mL; C. albicans, with an MFC of 50 µL/mL and M. multiflora (C) against C. albicans; and C. krusei, with a MFC of 50 µL/mL.     

ESI-MS/MS Analysis of Phenolic Compounds from Aeonium arboreum Leaf Extracts and Evaluation of their Antioxidant and Antimicrobial Activities

Aeonium is a genus of succulents belonging to the Crassulaceae family. Their importance in traditional medicine has stimulated both pharmacological and chemical research. In this study, we optimized extraction, separation, and analytical conditions using a high performance liquid chromatographic method coupled with electrospray ionization mass spectrometry by the negative mode (HPLC-ESI-MS) in order to, for the first time, determine thirty-four compounds from Aeonium arboreum leaves. Twenty-one of them are assigned among which are sixteen flavonoids and five phenolic acids. FRAP, TAC, DPPH, and ABTS^•+ radical scavenging were used to evaluate antioxidant activity. The obtained IC₅₀ values ranged from 0.031 to 0.043 mg.mL⁻¹ for DPPH and between 0.048 and 0.09 mg·mL⁻¹ for ABTS^•+. Antimicrobial activity was also assessed. The obtained minimum inhibitory concentrations (MIC) of these extracts ranged from 12.5 to 50 µg·mL⁻¹ against Micrococcus luteus, Listeria ivanovii, Staphylococcus aureus, Salmonella enterica, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, and Fusarium oxysporum, and from 25 to 50 µg·mL⁻¹ against Candida albicans. Therefore, these extracts can be considered as a potential source of biological active compounds.     

Photodynamic Inactivation Using Natural Bioactive Compound Prevents and Disrupts the Biofilm Produced by Staphylococcus saprophyticus

Staphylococcus saprophyticus, the food-borne bacteria present in dairy products, ready-to-eat food and environmental sources, has been reported with antibiotic resistance, raising concerns about food microbial safety. The antimicrobial resistance of S. saprophyticus requires the development of new strategies. Light- and photosensitizer-based antimicrobial photodynamic inactivation (PDI) is a promising approach to control microbial contamination, whereas there is limited information regarding the effectiveness of PDI on S. saprophyticus biofilm control. In this study, PDI mediated by natural bioactive compound (curcumin) associated with LED was evaluated for its potential to prevent and disrupt S. saprophyticus biofilms. Biofilms were treated with curcumin (50, 100, 200 µM) and LED fluence (4.32 J/cm², 8.64 J/cm², 17.28 J/cm²). Control groups included samples treated only with curcumin or light, and samples received neither curcumin nor light. The action was examined on biofilm mass, viability, cellular metabolic activity and cytoplasmic membrane integrity. PDI using curcumin associated with LED exhibited significant antibiofilm activities, inducing biofilm prevention and removal, metabolic inactivation, intracellular membrane damage and cell death. Likewise, scanning electronic microscopy observations demonstrated obvious structural injury and morphological alteration of S. saprophyticus biofilm after PDI application. In conclusion, curcumin is an effective photosensitizer for the photodynamic control of S. saprophyticus biofilm.     

Design,Synthesis, and Antimicrobial Activity of Certain New Indole-1,2,4 Triazole Conjugates

The increasing prevalence of microbial infections and the emergence of resistance to the currently available antimicrobial drugs urged the development of potent new chemical entities with eminent pharmacokinetic and/or pharmacodynamic profiles. Thus, a series of new indole-triazole conjugates 6a-u was designed and synthesized to be assessed as new antimicrobial candidates using the diameter of the inhibition zone and minimum inhibitory concentration assays against certain microbial strains. Their in vitro antibacterial evaluation revealed good to moderate activity against most of the tested Gram-negative strains with diameter of the inhibition zone (DIZ) values in the range of 11–15 mm and minimum inhibition concentration (MIC) values around 250 µg/mL. Meanwhile, their in vitro antifungal evaluation demonstrated a potent activity against Candida tropicalis with MIC value as low as 2 µg/mL for most of the tested compounds. Moreover, compound 6f is the most potent congener with an MIC value of 2 µg/mL against Candida albicans.     

Determination of 77 Multiclass Pesticides and Their Metabolitesin Capsicum and Tomato Using GC-MS/MS and LC-MS/MS

A quick, sensitive, and reproducible analytical method for the determination of 77 multiclass pesticides and their metabolites in Capsicum and tomato by gas and liquid chromatography tandem mass spectrometry was standardized and validated. The limit of detection of 0.19 to 10.91 and limit of quantification of 0.63 to 36.34 µg·kg⁻¹ for Capsicum and 0.10 to 9.55 µg·kg⁻¹ (LOD) and 0.35 to 33.43 µg·kg⁻¹ (LOQ) for tomato. The method involves extraction of sample with acetonitrile, purification by dispersive solid phase extraction using primary secondary amine and graphitized carbon black. The recoveries of all pesticides were in the range of 75 to 110% with a relative standard deviation of less than 20%. Similarly, the method precision was evaluated interms of repeatability (RSDr) and reproducibility (RSD_wR) by spiking of mixed pesticides standards at 100 µg·kg⁻¹ recorded anRSD of less than 20%. The matrix effect was acceptable and no significant variation was observed in both the matrices except for few pesticides. The estimated measurement uncertainty found acceptable for all the pesticides. This method found suitable for analysis of vegetable samples drawn from market and farm gates.     

Interaction between Curcumin and β-Casein: Multi-Spectroscopic and Molecular Dynamics Simulation Methods

Effect of temperature and pH on the interaction of curcumin with β-casein was explored by fluorescence spectroscopy, ultraviolet-visible spectroscopy and molecular dynamics simulation. The spectroscopic results showed that curcumin could bind to β-casein to form a complex which was driven mainly by electrostatic interaction. The intrinsic fluorescence of β-casein was quenched by curcumin through static quenching mechanism. The binding constants of curcumin to β-casein were 6.48 × 10⁴ L/mol (298 K), 6.17 × 10⁴ L/mol (305 K) and 5.73 × 10⁴ L/mol (312 K) at pH 2.0, which was greater than that (3.98 × 10⁴ L/mol at 298 K, 3.90 × 10⁴ L/mol at 305 K and 3.41 × 10⁴ L/mol at 312 K) at pH 7.4. Molecular docking study showed that binding energy of β-casein-curcumin complex at pH 2.0 (−7.53 kcal/mol) was lower than that at pH 7.4 (−7.01 kcal/mol). The molecular dynamics simulation study showed that the binding energy (−131.07 kJ/mol) of β-casein-curcumin complex was relatively low at pH 2.0 and 298 K. α-Helix content in β-casein was decreased and random coil content was increased in the presence of curcumin. These results can promote a deep understanding of interaction between curcumin and β-casein and provide a reference for improving the bioavailability of curcumin.     

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e–f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl₂ or 5f with 3,4-Cl₂). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC₅₀ = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160–4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-N,N′,N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.     

Chemical Constituents of the Essential Oil from Ecuadorian Endemic Species Croton ferrugineus and Its Antimicrobial,Antioxidant and α-Glucosidase Inhibitory Activity

Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), β-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 μg/mL, a scavenging capacity SC₅₀ of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC₅₀ of 146 ± 20 µg/mL.     

In-Vitro Screenings for Biological and Antioxidant Activities of Water Extract from Theobroma cacao L. Pod Husk: Potential Utilization in Foods

Increasing production of cocoa (Theobroma cacao L.) leads to a higher environmental burden due to its solid waste generation. Cocoa pod husk, one of the major solid wastes of cocoa production, contains rich bioactive compounds unveiling its valorization potential. With that in mind, our research aimed to explore the biological and antioxidant activities of aqueous extracts from cocoa pod husks. In this present work, cocoa pod husk was extracted using water and subsequentially partitioned using n-hexane, ethyl acetate, and methanol. The antimicrobial investigation revealed that the ethyl acetate solubles were active against the Staphylococcus aureus, Escherichia coli, and Candida albicans, where at a 20% w/v concentration, the inhibition diameters were 6.62 ± 0.10, 6.52 ± 0.02, and 11.72 ± 0.36 mm, respectively. The extracts were found non-toxic proven by brine shrimp lethality tests against Artemia salina with LC₅₀ scores ranging from 74.1 to 19,054.6 μg/mL. The total phenolic content and total flavonoid content were obtained in the range of 47.44 to 570.44 mg/g GAE and 1.96 to 4.34 mg/g QE, respectively. Antioxidant activities of the obtained extracts were revealed by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay with EC₅₀ reached as low as 9.61 μg/mL by the ethyl acetate soluble. Phytochemical screening based on gas chromatography—mass spectroscopy analysis on the sample with the highest antioxidant activities revealed the dominant presence of three phytosterols, namely gamma-sitosterol, stigmasterol, and campesterol.     

Antioxidant,Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC₅₀ of 1.30 ± 0.05 mg/mL in the DPPH test and an EC₅₀ equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC₅₀) was 7.8 ± 0.3 μL EO/L, while the effective concentration in the ingestion test (LC₅₀) was 15.0 ± 2.1 μL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.     

Phytochemical Profile,Antimicrobial, Cytotoxic,and Antioxidant Activities of Fresh and Air-Dried Satureja nabateorum Essential Oils

Satureja nabateorum (Danin and Hedge) Bräuchler is a perennial herb in the Lamiaceae family that was discovered and classified in 1998. This green herb is restricted to the mountains overlooking the Dead Sea, specifically in Jordan’s southwest, the Edom mountains, and the Tubas mountains in Palestine. Gas chromatography-mass spectrometry (GC-MS) analysis of essential oil (EO) of air-dried and fresh S. nabateorum resulted in the identification of 30 and 42 phytochemicals accounting for 99.56 and 98.64% of the EO, respectively. Thymol (46.07 ± 1.1 and 40.64 ± 1.21%) was the major compound, followed by its biosynthetic precursors γ-terpinene (21.15 ± 1.05% and 20.65 ± 1.12%), and p-cymene (15.02 ± 1.02% and 11.51 ± 0.97%), respectively. Microdilution assay was used to evaluate the antimicrobial property of EOs against Staphylococcus aureus (ATCC 25923), clinical isolate Methicillin-Resistant Staphylococcus aureus (MRSA), Enterococcus faecium (ATCC 700221) Klebsiella pneumoniae (ATCC 13883), Proteus vulgaris (ATCC 700221), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC-90028). With a MIC of 0.135 μg/mL, the EOs has the most potent antibacterial action against K. pneumonia. Both EOs display good antifungal efficacy against C. albicans, with a MIC value of 0.75 μg/mL, which was better than that of Fluconazole’s (positive control, MIC = 1.56 μg/mL). The antioxidant capacity of EOs extracted from air-dried and fresh S. nabateorum was determined using the DPPH assay, with IC₅₀ values of 4.78 ± 0.41 and 5.37 ± 0.40 μg/mL, respectively. The tested EOs showed significant cytotoxicity against Hela, HepG2, and COLO-205 cells, with IC₅₀ values ranging from 82 ± 0.98 to 256 ± 1.95 μg/mL. The current work shows there is a possibility to use the S. nabateorum EOs for various applications.     

Resistant Starch Contents of Starch Isolated from Black Longan Seeds

A large quantity of longan fruits (Dimocarpus longan Lour.) produced annually are processed into many products, one of which is black longan, from which the dried, dark-brown meat has been used medicinally in traditional medicine, while the starch-containing seeds are discarded. In this study, starch samples (BLGSs) were isolated from seeds of black longan fruits prepared using varied conditions. The in vitro digestibility was determined in comparison with those extracted from fresh (FLGS) and dried (DLGS) seeds. Scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy were employed to evaluate the starch properties. The results showed that the yields of FLGS, DLGS, and BLGSs were 20%, 23%, and 16–22% w/w, respectively. SEM images showed starch granules of mixed shapes, with sizes up to 15 µm in all samples. XRD patterns confirmed an A-type crystallinity for FLGS and DLGS, with strong refraction peaks at 2θ = 15°, 17°, 18°, and 23°, while BLGSs also showed detectable peaks at 2θ = 10° and 21°, which suggested V-type structures. Thermal properties corroborated the changes by showing increases in peak gelatinization temperature (T_p) and enthalpy energy (ΔH) in BLGSs. The paste viscosity of BLGSs (5% w/w) decreased by 20–58% from that of FLGS. The FTIR peak ratio at 1045/1022 and 1022/995 cm⁻¹ also indicated an increase in ordered structure in BLGSs compared to FLGS. The significant increase in the amounts of slowly digestible starch (SDS) and resistant starch (RS) in BLGSs compared to FLGS, especially at a prolonged incubation time of 20 (4.2×) and 30 days (4.1×), was proposed to be due to the heat-induced formation of starch inclusion with other components inside the seed during the black longan production process. Thus, black longan seed could be a new source of starch, with increased RS content, for potential use in the food and related industries.     

In Vitro Antileishmanial and Antitrypanosomal Activities of Plicataloside Isolated from the Leaf Latex of Aloe rugosifolia Gilbert & Sebsebe (Asphodelaceae)

Trypanosomiasis and leishmaniasis are among the major neglected diseases that affect poor people, mainly in developing countries. In Ethiopia, the latex of Aloe rugosifolia Gilbert & Sebsebe is traditionally used for the treatment of protozoal diseases, among others. In this study, the in vitro antitrypanosomal activity of the leaf latex of A. rugosifolia was evaluated against Trypanosoma congolense field isolate using in vitro motility and in vivo infectivity tests. The latex was also tested against the promastigotes of Leishmania aethiopica and L. donovani clinical isolates using alamar blue assay. Preparative thin-layer chromatography of the latex afforded a naphthalene derivative identified as plicataloside (2,8-O,O-di-(β-D-glucopyranosyl)-1,2,8-trihydroxy-3-methyl-naphthalene) by means of spectroscopic techniques (HRESI-MS, ¹H, ¹³C-NMR). Results of the study demonstrated that at 4.0 mg/mL concentration plicataloside arrested mobility of trypanosomes within 30 min of incubation period. Furthermore, plicataloside completely eliminated subsequent infectivity in mice for 30 days at concentrations of 4.0 and 2.0 mg/mL. Plicataloside also displayed antileishmanial activity against the promastigotes of L. aethopica and L. donovani with IC₅₀ values 14.22 ± 0.41 µg/mL (27.66 ± 0.80 µM) and 18.86 ± 0.03 µg/mL (36.69 ± 0.06 µM), respectively. Thus, plicataloside may be used as a scaffold for the development of novel drugs effective against trypanosomiasis and leishmaniasis.     

Discovery of New Coumarin-Based Lead with Potential Anticancer,CDK4 Inhibition and Selective Radiotheranostic Effect: Synthesis, 2D & 3D QSAR,Molecular Dynamics,In Vitro Cytotoxicity,Radioiodination, and Biodistribution Studies

Novel 6-bromo-coumarin-ethylidene-hydrazonyl-thiazolyl and 6-bromo-coumarin-thiazolyl-based derivatives were synthesized. A quantitative structure activity relationship (QSAR) model with high predictive power r² = 0.92, and RMSE = 0.44 predicted five compounds; 2b, 3b, 5a, 9a and 9i to have potential anticancer activities. Compound 2b achieved the best ΔG of –15.34 kcal/mol with an affinity of 40.05 pki. In a molecular dynamic study 2b showed an equilibrium at 0.8 Å after 3.5 ns, while flavopiridol did so at 0.5 Å after the same time (3.5 ns). 2b showed an IC₅₀ of 0.0136 µM, 0.015 µM, and 0.054 µM against MCF-7, A-549, and CHO-K1 cell lines, respectively. The CDK4 enzyme assay revealed the significant CDK4 inhibitory activity of compound 2b with IC₅₀ of 0.036 µM. The selectivity of the newly discovered lead compound 2b toward localization in tumor cells was confirmed by a radioiodination biological assay that was done via electrophilic substitution reaction utilizing the oxidative effect of chloramine-t. ¹³¹I-2b showed good in vitro stability up to 4 h. In solid tumor bearing mice, the values of tumor uptake reached a height of 5.97 ± 0.82%ID/g at 60 min p.i. ¹³¹I-2b can be considered as a selective radiotheranostic agent for solid tumors with promising anticancer activity.     

Design of Turmeric Rhizome Extract Nano-Formula for Delivery to Cancer Cells

Novel turmeric rhizome extract nanoparticles (TE-NPs) were developed from fractions of dried turmeric (Curcuma longa Linn.) rhizome. Phytochemical studies, by using HPLC and TLC, of the fractions obtained from ethanol extraction and solvent–solvent extraction showed that turmeric rhizome ethanol extract (EV) and chloroform fraction (CF) were composed mainly of three curcuminoids and turmeric oil. Hexane fraction (HE) was composed mainly of turmeric oil while ethyl acetate fraction (EA) was composed mainly of three curcuminoids. The optimal TE-NPs formulation with particle size of 159.6 ± 1.7 nm and curcumin content of 357.48 ± 8.39 µM was successfully developed from 47-run D-optimal mixture–process variables experimental design. Three regression models of z-average, d₅₀, and d₉₀ could be developed with a reasonable accuracy of prediction (predicted r² values were in the range of 0.9120–0.9992). An in vitro cytotoxicity study using MTT assay demonstrated that the optimal TE-NPs remarkably exhibited the higher cytotoxic effect on human hepatoma cells, HepG2, when compared with free curcumin. This study is the first to report nanoparticles prepared from turmeric rhizome extract and their cytotoxic activity to hepatic cancer cells compared with pure curcumin. These nanoparticles might serve as a potential delivery system for cancer therapy.     

Study on the Joint Toxicity of BPZ,BPS, BPC and BPF to Zebrafish

Bisphenol Z (BPZ), bisphenol S (BPS), bisphenol C (BPC), and bisphenol F (BPF) had been widely used as alternatives to bisphenol A (BPA), but the toxicity data of these bisphenol analogues were very limited. In this study, the joint toxicity of BPZ, BPS, BPC, and BPF to zebrafish (Danio rerio) was investigated. The median half lethal concentrations (LC50) of BPZ, BPS, BPC, and BPF to zebrafish for 96 h were 6.9 × 10⁵ µM, 3.9 × 10⁷ µM, 7.1 × 10⁵ µM, and1.6 × 10⁶ µM, respectively. The joint toxicity effect of BPF–BPC (7.7 × 10⁵–3.4 × 10⁵µM) and BPZ–BPC (3.4 × 10⁵–3.5 × 10⁵µM) with the same toxic ratio showed a synergistic effect, which may be attributed to enzyme inhibition or induction theory. While the toxicity effect of the other two bisphenol analogue combined groups and multi-joint pairs showed an antagonistic effect due to the competition site, other causes need to be further explored. Meanwhile, the expression levels of the estrogen receptor genes (ERα, ERβ1) and antioxidant enzyme genes (SOD, CAT, GPX) were analyzed using a quantitative real-time polymerase chain reaction in zebrafish exposure to LC₅₀ of BPZ, BPS, BPC, and BPF collected at 24, 48, 72, and 96 h. Relative expression of CAT, GPX, and ERβ1 mRNA declined significantly compared to the blank control, which might be a major cause of oxidant injury of antioxidant systems and the disruption of the endocrine systems in zebrafish.