Search Results (50)

Lawsonia inermis L. is renowned for its hair dyeing properties, with henna quality and safety often regulated by restrictions on the lawsone (2-hydroxy-1,4-naphthoquinone) content. In henna leaves, lawsone exists as glycosylated precursors, hennosides A, B, and C. Aqueous maceration revealed the sensitivity of enzymatic lawsone release, while ethanol extraction inhibited β-glucosidase activity, enabling controlled hennoside extraction. Hennoside A was isolated via RP-column chromatography and characterized using ESI-TOF, ¹H-/¹³C-NMR, COSY, NOESY, HSQC, and HMBC. The purified compound proved suitable as an HPLC reference standard. The acidic hydrolysis of hennoside-rich extracts highlighted the limitations of lawsone-based analysis, underscoring glycosylated precursors as more reliable quality markers. Lawsone quantification via enzymatic or acid catalysis demonstrated varying accuracy in quality control. A hennoside-based approach ensures consistency by estimating the maximum releasable lawsone without inducing its formation, providing a more robust metric for a henna quality assessment. Full article

In this study, we examined the oxidation of (E)-2-hydroxy-1-naphthaldehyde oxime with lead tetraacetate in tetrahydrofuran that produced novel (E)-7a,8,9,10-tetrahydro-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazin-12-one oxime and 1-(pyrrolidin-1-yl)naphtho[1,2-d]isoxazole and known 7a,8,9,10-tetrahydro-12H-naphtho[1,2-e]pyrrolo-[2,1-b][1,3]oxazin-12-one in 15, 18, and 10% yields, respectively. The oxime is partially hydrolyzed to its corresponding ketone. Modifying the oxidants and reaction conditions did not improve the product yields. Based on previous studies in our laboratory, we proposed that the reactions proceed via the formation of an o-naphthoquinone nitrosomethide intermediate; 1D and 2D NMR, HRMS, IR, and UV-VIS spectra provided information that supported the structure of the products. Full article

Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) is a naturally occurring compound with known anticancer properties, and its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance their therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles and their effects on apoptosis in colorectal cancer cells. Les-6547 and Les-6557 increased the population of ROS-positive HT-29 cancer cells approximately 10-fold compared with control cells (36.3% and 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated with cell cycle arrest, inhibition of DNA biosynthesis, and reduced cell proliferation. A significant shift in the cell cycle distribution was observed, with an increase in S-phase (from 17.3% in the control to 34.7% to 51.3% for Les-6547 and Les-6557, respectively) and G2/M phase (from 24.3% to 39.9% and 28.8%). Additionally, Les-6547 and Les-6557 inhibited DNA biosynthesis in HT-29 cells, with IC₅₀ values of 2.21 µM and 2.91 µM, respectively. Additionally, ROS generation may initiate the intrinsic apoptotic pathway. Les-6547 and Les-6557 activated both intrinsic and extrinsic apoptotic pathways, demonstrated by notable increases in the activity of caspase 3/7, 8, 9, and 10. This study provides a robust basis for investigating the detailed molecular mechanisms of action and therapeutic potential of Les-6547 and Les-6557. Full article

There is a strong demand for new and efficient antiviral compounds. A series of 2-hydroxy-1,4-naphthoquinone Mannich bases were screened for their HIV-1-RNase H inhibitory activity. An HIV-1-RNase H assay was used to study the RNase H inhibition by the test compounds. Docking of active derivatives into the active site of the enzyme was carried out. Compounds 1e and 2k showed distinctly higher HIV-1-RNase H inhibitory activity (IC₅₀ = 2.8–3.1 µM) than the known inhibitors RDS1759 and compound 13. The binding mode and possible interactions of 1e and 2k with the HIV-1-RNase H active site were determined using molecular docking, which led to the identification of salient and concealed pharmacophoric features of these molecules. The docking analysis revealed that there are significant differences in the binding mode of these compounds within the active site of the target enzyme. A selection of HIV-1-RNase H-inhibitory Mannich bases was tested for antiviral activity against HIV-1, and compound 2k showed the highest activity at low toxicity to host cells. The lawsone Mannich bases 1e and 2k also underwent a preliminary screening for activity against SARS-CoV-2, and compound 1e was found to inhibit SARS-CoV-2 replication (IC₅₀ = 11.2 µM). Full article

E. coli nitroreductase A (NfsA) is a candidate for gene-directed prodrug cancer therapy using bioreductively activated nitroaromatic compounds (ArNO₂). In this work, we determined the standard redox potential of FMN of NfsA to be −215 ± 5 mV at pH 7.0. FMN semiquinone was not formed during 5-deazaflavin-sensitized NfsA photoreduction. This determines the two-electron character of the reduction of ArNO₂ and quinones (Q). In parallel, we characterized the oxidant specificity of NfsA with an emphasis on its structure. Except for negative outliers nitracrine and SN-36506, the reactivity of ArNO₂ increases with their electron affinity (single-electron reduction potential, E¹₇) and is unaffected by their lipophilicity and Van der Waals volume up to 386 Å. The reactivity of quinoidal oxidants is not clearly dependent on E¹₇, but 2-hydroxy-1,4-naphthoquinones were identified as positive outliers and a number of compounds with diverse structures as negative outliers. 2-Hydroxy-1,4-naphthoquinones are characterized by the most positive reaction activation entropy and the negative outlier tetramethyl-1,4-benzoquinone by the most negative. Computer modelling data showed that the formation of H bonds with Arg15, Arg133, and Ser40, plays a major role in the binding of oxidants to reduced NfsA, while the role of the π–π interaction of their aromatic structures is less significant. Typically, the calculated hydride-transfer distances during ArNO₂ reduction are smallwer than for Q. This explains the lower reactivity of quinones. Another factor that slows down the reduction is the presence of positively charged aliphatic substituents. Full article

Low-molecular-weight protein tyrosine phosphatases (LMW-PTPs) are involved in promoting the intracellular survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis. These PTPs directly alter host signalling pathways to evade the hostile environment of macrophages and avoid host clearance. Among these, protein tyrosine phosphatase A (Mt-PTPa) is implicated in phagosome acidification failure, thereby inhibiting phagosome maturation to promote Mycobacterium tuberculosis (Mtb) survival. In this study, we explored Mt-PTPa as a potential drug target for treating Mtb. We started by screening a library of 502 pure natural compounds against the activities of Mt-PTPa in vitro, with a threshold of 50% inhibition of activity via a <500 µM concentration of the candidate drugs. The initial screen identified epigallocatechin, myricetin, rosmarinic acid, and shikonin as hits. Among these, the naphthoquinone, shikonin (5, 8-dihydroxy-2-[(1R)-1-hydroxy-4-methyl-3-pentenyl]-1,4-naphthoquinone), showed the strongest inhibition (IC₅₀ 33 µM). Further tests showed that juglone (5-hydroxy-1,4-naphthalenedione), another naphthoquinone, displayed similar potent inhibition of Mt-PTPa to shikonin. Kinetic analysis of the inhibition patterns suggests a non-competitive inhibition mechanism for both compounds, with inhibitor constants (Ki) of 8.5 µM and 12.5 µM for shikonin and juglone, respectively. Our findings are consistent with earlier studies suggesting that Mt-PTPa is susceptible to specific allosteric modulation via a non-competitive or mixed inhibition mechanism. Full article

Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development. Full article

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, PLB), a naturally occurring naphthoquinone mainly isolated from the plant Plumbago zeylanica L., has been proven to possess anticancer activities towards multiple types of cancer. Although there has been an increasing amount of research regarding its anticancer effects, the association between oxidative stress, genotoxicity and the cell cycle arrest induced by PLB still remains unclear. Therefore, it is important to investigate their potential connections and the involvement of DNA damage and the ataxia telangiectasia mutated protein (ATM)-p53 signaling pathway in PLB’s anticancer mechanism. The present study showed that PLB exposure significantly reduced HCC cell viability and colony formation. In addition, PLB-induced G2/M cell cycle arrest, oxidative stress, and DNA damage was detected, which could be almost blocked by NAC pretreatment. PLB could trigger a DNA damage response by activating cell cycle checkpoints such as ATM, checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2) and p53. Meanwhile, the key modulator of the G2/M transition factor, Cell Division Cycle 25C (cdc25C), was significantly downregulated in an ROS-dependent manner. Furthermore, pretreatment with ATM and p53 inhibitors (KU55933 and Pifithrin-α) could reduce the occurrence of G2/M cell cycle arrest by inhibiting the activation of the ATM-p53 pathway. Taken together, these results indicate that ROS-mediated oxidative stress plays a key role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway. Full article

The aim of this study was to evaluate the possible effects of a 50 Hz electric field on brain tissue and the positive effects of juglone (5-hydroxy-1,4-naphthoquinone) antioxidant activity, using the immunohistochemical technique on male Wistar-Albino rats. The effects on blood tissue were also examined using biochemical, physiological and comet methods. Animals were randomly divided into three groups (eight in each group): group I: control, group II: electric field, group III: 50 Hz electric field + juglone (5-hydroxy-1,4-naphthoquinone)/300 ppm. Juglone was applied per day by gavage over 30 days. At the end of the experimental procedure, animals were sacrificed and brain tissue was subjected to routine histologic and immunohistochemical processes. As a result of histophatological examination, the brain tissue of rats with 50 Hz electric field exposure showed severe histopathological changes. The differences between groups were statistically significant according to total comet score (p = 0.001). For the antioxidant parameters on the blood, SOD activity in the electric field group was significantly higher among the other groups, although we did not find significant differences in MDA, CAT activity level. Full article

Although heavy metals are naturally occurring elements that are found throughout the Earth’s crust, most environmental contamination and human exposure result from anthropogenic activities, such as mining and smelting operations, industrial production and use, and the domestic and agricultural use of metals and metal-containing compounds. The accumulation of heavy metals eventually produces reactive oxygen species that can cause oxidative stress, which may lead to the production of various diseases. The aim of this study was to evaluate the possible effects of iron and zinc on kidney and liver tissues and the positive effects of juglone (5-hydroxy-1,4-naphthoquinone) antioxidant activity, using an immunohistochemical technique. The animals under study were randomly divided into five groups (seven in each group): group I, control; group II, iron (Fe) (600 ppm); group III, zinc (Zn) (400 ppm); group IV, Fe + antioxidant juglone; and group V, Zn + antioxidant juglone. Hematoxylin-eosin (H&E) was applied to determine the histological sides of the damage caused by the heavy metals in the liver and kidney tissues and the effects of the administration of juglone on reducing these damages. Furthermore, the immunohistochemical TUNEL method was applied to determine the DNA damages in the cells. The density of the damage in the liver and kidney tissues of the iron group was higher than in the other groups. Full article

The consumption of fresh vegetables has been consistently associated with numerous health benefits. However, several factors (such as allelochemicals) influence yield, quality, and metabolites, which inevitably affect the fruit quality and health benefits. The present study was conducted to investigate the yield, quality, metabolic responses, and potential toxicity of Cucumis sativus grown in juglone-containing soils. For the treatments, pure juglone (100 µM, 1 mM) and walnut leaf extracts (100 µM) in soil concentrations found in walnut orchards were used. A total of 36 phenolic compounds were identified and quantified in fruits, leaves, and roots using a mass spectrometer coupled with high-performance liquid chromatography. We concluded that juglone at a concentration of 100 µM or walnut leaf extract at the same juglone concentration does not affect the yield of C. sativus, while juglone at a concentration of 1 mM strongly affects it. In the case of juglone, juglone itself was found only in the roots of C. sativus, but not in the leaves or fruits, so C. sativus fruits are considered safe for cultivation in juglone-containing soils. However, this could prove problematic if the plants grown are tubers or root vegetables. The data suggest that juglone itself inhibits secondary metabolism in the plant, making it more susceptible to stress and pathogen attacks. Full article

Marine-derived Streptomyces actinomycetes are one of the most important sources for the discovery of novel bioactive natural products. This study characterized the isolation, structural elucidation and biological activity evaluation of thirty compounds, including twelve previously undescribed compounds, namely hygrocins K–U (5–13, 17 and 18) and streptophenylpropanamide A (23), from the marine-associated actinomycete Streptomyces sp. ZZ1956. Structures of the isolated compounds were determined by a combination of extensive NMR spectroscopic analyses, HRESIMS data, the Mosher’s method, ECD calculations, single crystal X-ray diffraction and comparison with reported data. Hygrocins C (1), D (2), F (4), N (8), Q (11) and R (12), 2-acetamide-6-hydroxy-7-methyl-1,4-naphthoquinone (22), echoside C (27), echoside A (28) and 11,11′-O-dimethylelaiophylin (30) had antiproliferative activity (IC₅₀: 0.16–19.39 μM) against both human glioma U87MG and U251 cells with hygrocin C as the strongest active compound (IC₅₀: 0.16 and 0.35 μM, respectively). The analysis of the structure–activity relationship indicated that a small change in the structures of the naphthalenic ansamycins had significant influence on their antiglioma activities. Hygrocins N (8), O (9), R (12), T (17) and U (18), 2-amino-6-hydroxy-7-methyl-1,4-naphthoquinone (21), 2-acetamide-6-hydroxy-7-methyl-1,4-naphthoquinone (22), 3′-methoxy(1,1′,4′,1″-terphenyl)-2′,6′-diol (26), echoside C (27) and echoside A (28) showed antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli with MIC values of 3–48 μg/mL. Full article

Skin diseases are commonly treated with antihistamines, antibiotics, laser therapy, topical medications, local vitamins, or steroids. Since conventional treatments for wound healing (skin allografts, amnion, xenografts, etc.) have disadvantages such as antigenicity of the donor tissue, risk of infection, or lack of basement membrane, skin tissue engineering has become a popular new approach. The current study presents the design and fabrication of a new wound-dressing material by the addition of Juglone (5-hydroxy-1,4-naphthoquinone) to a 25% Polycaprolactone (PCL) scaffold. Juglone (J) is a significant allelochemical found in walnut trees and, in this study is used as a bioactive material. The effects of different amounts of J (1.25, 2.5, 5, 7.5, and 10 mg) on the biocompatibility, mechanical, chemical, thermal, morphological, and antimicrobial properties of the 3D-printed 25% PCL scaffolds were investigated. The addition of J increased the pore diameter of the 25% PCL scaffold. The maximum pore size (290.72 ± 14 µm) was observed for the highest amount of J (10 mg). The biocompatibility tests on the scaffolds demonstrated biocompatible behavior from the first day of incubation, the 25% PCL/7.5 J scaffold having the highest viability value (118%) among all of the J-loaded scaffolds. Drug release of J into phosphate buffered saline (PBS) at pH 7.4 showed that J was completely released from all 25% PCL/J scaffolds within 7 days of incubation. Full article

It was previously shown that the antitumor and cytotoxic activity of the essential oil (EO) extracted from the aerial parts of Glandora rosmarinifolia appears to involve a pro-oxidant mechanism in hepatocellular carcinoma (HCC) and in triple-negative breast cancer (TNBC) cell lines. Its most abundant compound is a hydroxy-methyl-naphthoquinone isomer. Important pharmacological activities, such as antitumor, antibacterial, antifungal, antiviral and antiparasitic activities, are attributed to naphthoquinones, probably due to their pro-oxidant or electrophilic potential; for some naphthoquinones, a mechanism of action of topoisomerase inhibition has been reported, in which they appear to act both as catalytic inhibitors and as topoisomerase II poisons. Our aim was to evaluate the cytotoxic activity of the essential oil on an acute myeloid leukemia cell line HL-60 and on its multidrug-resistant (MDR) variant HL-60R and verify its ability to interfere with topoisomerase II activity. MTS assay showed that G. rosmarinifolia EO induced a decrease in tumor cell viability equivalent in the two cell lines; this antitumor effect could depend on the pro-oxidant activity of EO in both cell lines. Furthermore, G. rosmarinifolia EO reduced the activity of Topo II in the nuclear extracts of HL-60 and HL-60R cells, as inferred from the inability to convert the kinetoplast DNA into the decatenated form and then not inducing linear kDNA. Confirming this result, flow cytometric analysis proved that EO induced a G₀-G₁ phase arrest, with cell reduction in the S-phase. In addition, the combination of EO with etoposide showed a good potentiation effect in terms of cytotoxicity in both cell lines. Our results highlight the antitumor activity of EO in the HL-60 cell line and its MDR variant with a peculiar mechanism as a Topo II modulator. Unlike etoposide, EO does not cause stabilization of a covalent Topo II-DNA intermediate but acts as a catalytic inhibitor. These data make G. rosmarinifolia EO a potential anticancer drug candidate due to its cytotoxic action, which is not affected by multidrug resistance. Full article

Neurodegenerative diseases present an increasing problem as the world’s population ages; thus, the discovery of new drugs that prevent diseases such as Alzheimer’s, and Parkinson’s diseases are vital. In this study, Rhinacanthin-C and -D were isolated from Rhinacanthus nasustus, using ethyl acetate, followed by chromatography to isolate Rhinacanthin-C and -D. Both compounds were confirmed using NMR and ultra-performance-LCMS. Using glutamate toxicity in HT-22 cells, we measured cell viability and apoptosis, ROS build-up, and investigated signaling pathways. We show that Rhinacanthin-C and 2-hydroxy-1,4-naphthoquinone have neuroprotective effects against glutamate-induced apoptosis in HT-22 cells. Furthermore, we see that Rhinacanthin-C resulted in autophagy inhibition and increased ER stress. In contrast, low concentrations of Rhinacanthin-C and 2-hydroxy-1,4-naphthoquinone prevented ER stress and CHOP expression. All concentrations of Rhinacanthin-C prevented ROS production and ERK1/2 phosphorylation. We conclude that, while autophagy is present in HT-22 cells subjected to glutamate toxicity, its inhibition is not necessary for cryoprotection. Full article