Chemistry of naphthazarin derivatives: XV. Bromination of naphthazarin and its derivatives

Bromination of a number of naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) derivatives having different substituents in the aromatic ring with molecular bromine in carbon tetrachloride was studied. Preparative procedures for the synthesis of 2-bromo-5,8-dihydroxy-7-methoxy-1,4-naphthoquinone, 2-bromo-6,7-dichloro-5,8-dihydroxy-1,4-naphthoquinone, 2-bromo-3,5,8-trihydroxy-1,4-naphthoquinone, and 2-bromo-6,7-dichloro-3,5,8-trihydroxy-1,4-naphthoquinone were developed.     

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.     

Photoreactions of 1,4-Naphthoquinones: effects of substituents and water on the intermediates and reactivity

The photochemistry of lapachol and other 1,4-naphthoquinone (NQ) derivatives, e.g. 2-methoxy-1,4-naphthoquinone (MeONQ), 2-hydroxy-1,4-naphthoquinone (2-HONQ) or 5-hydroxy-1,4-naphthoquinone (5-HONQ) and 2-methyl-5-hydroxy-1,4-naphthoquinone (P-NQ) in solution at room temperature was studied by ultraviolet-visible spectroscopy after nanosecond laser pulses at 248 nm. The triplet state and semiquinone radicals were observed for MeONQ, HONQ and P-NQ, whereas for lapachol, intramolecular H-atom and charge transfer processes take place, as in the case of vitamin K1. The photoinduced reaction of NQ into HONQ is initiated by nucleophilic water addition to the triplet state, and for the secondary reactions, a modified mechanism is proposed.     

Activity-directed-fractionation and isolation of four antibacterial compounds from Abrus precatorius L., roots

Root extracts of the plant Abrus precatorius L., was tested for antibacterial activity. Various solvent fractions exhibited inhibitory activity against 13 gram-positive and gram-negative bacteria. Root extracts were analyzed by thin layer chromatography (TLC). The antibacterial activity was localized to specific chromatophores in the chloroform fraction through a bioautography assay. It was found localized to four chromatophores out of seven. The chromatophores were isolated from the TLC plates and rechecked for activity against Slaphylococcus aureus A, using a disc diffusion assay. Among the four active principles isolated, AP 3 (Rf 0.87) exhibited maximum activity i.e. 56% inhibition of growth of S. aureus A, in disc diffusion assay compared to the standard antibiotic Ampicillin. Results of this study suggest that chloroform extractable phytochemicals in A. precatorius L. may yield promising molecules with antibiotic activity.     

Selective cytotoxicity of goniothalamin against hepatoblastoma HepG2 cells

Liver cancer has become one of the major types of cancer with high mortality and liver cancer is not responsive to the current cytotoxic agents used in chemotherapy. The purpose of this study was to examine the in vitro cytotoxicity of goniothalamin on human hepatoblastoma HepG2 cells and normal liver Chang cells. The cytotoxicity of goniothalamin against HepG2 and liver Chang cell was tested using MTT cell viability assay, LDH leakage assay, cell cycle flow cytometry PI analysis, BrdU proliferation ELISA assay and trypan blue dye exclusion assay. Goniothalamin selectively inhibited HepG2 cells [IC?? = 4.6 (±0.23) μM in the MTT assay; IC?? = 5.20 (±0.01) μM for LDH assay at 72 hours], with less sensitivity in Chang cells [IC?? = 35.0 (±0.09) μM for MTT assay; IC?? = 32.5 (±0.04) μM for LDH assay at 72 hours]. In the trypan blue dye exclusion assay, the Viability Indexes were 52 ± 1.73% for HepG2 cells and 62 ± 4.36% for Chang cells at IC?? after 72 hours. Cytotoxicity of goniothalamin was related to inhibition of DNA synthesis, as revealed by the reduction of BrdU incorporation. At 72 hours, the lowest concentration of goniothalamin (2.3 μL) retained 97.6% of normal liver Chang cells proliferation while it reduced HepG2 cell proliferation to 19.8% as compared to control. Besides, goniothalamin caused accumulation of hypodiploid apoptosis and different degree of G2/M arrested as shown in cell cycle analysis by flow cytometry. Goniothalamin selectively killed liver cancer cell through suppression of proliferation and induction of apoptosis. These results suggest that goniothalamin shows potential cytotoxicity against hepatoblastoma HepG2 cells.     

Antioxidant and antiproliferative activity of Stachys glutinosa L. ethanol extract

Ethanol extracts of Stachys glutinosa L. (Lamiaceae) were investigated for antioxidative properties, as well as antiproliferative action on various cell lines. The antioxidant activities were investigated by ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid) assay, DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging, β-carotene/linoleic acid assay, scavenging of hydrogen peroxide (horseradish peroxidase test), superoxide anion scavenging, and hypochlorous acid scavenging (taurine test). The antioxidant activity was reported as IC₅₀ and reveals antioxidant effects. Antiproliferative effects were measured in vitro on three cell lines: HepG2 (human hepatocarcinoma), MCF7 (breast human adenocarcinoma) and C2C12 (mouse myoblast) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract induced variations in cell viability on all cell lines tested. At 200 μg/mL, the effects on cell viability were ? 23%, ? 27% and ? 37%, respectively, for C2C12, MCF7 and HepG2.     

Activity-directed fractionation and isolation of four antibacterial compounds from Abrus precatorius L. roots

Root extracts of the plant Abrus precatorius L. was tested for antibacterial activity. Various solvent fractions exhibited inhibitory activity against 13 gram-positive and gram-negative bacteria. Root extracts were analyzed by thin layer chromatography. The antibacterial activity was localized to specific chromatophores in the chloroform fraction through a bioautography assay. It was found localized to 4 chromatophores out of 7. The chromatophores were isolated from the TLC plates and rechecked for activity against Staphylococcus aureus A, using a disc diffusion assay. Among the four active principles isolated, AP 3 (Rf 0.87) exhibited maximum activity, i.e., 56% inhibition of growth of S. aureus A, in disc diffusion assay compared to the standard antibiotic Ampicillin. Results of this study suggest that chloroform extractable phytochemicals in A. precatorius L. may yield promising molecules with antibiotic activity.     

Design, synthesis, and anti-proliferative evaluation of [1,1'-biphenyl]-4-ols as inhibitor of HUVEC migration and tube formation

Allylated biphenol neolignans contain a variety of chemopreventive entities that have been used as anti-tumor drug leads. Herein, 37 allylated biphenols were evaluated for anti-proliferative activity by the MTT assay and inhibitory effect on the migration and tube formation of HUVECs featuring anti-angiogenic properties. 3-(2-Methylbut-3-en-2-yl)-3′,5′-bis(trifluoromethyl)-[1,1′-biphenyl]-4-ol (5c) exerted an inhibitory effect on HUVECs compared to honokiol (IC?? = 47.0 vs. 52.6 μM) and showed significant blocking effects on the proliferation of C26, Hela, K562, A549, and HepG2 (IC?? = 15.0, 25.0, 21.2, 29.5, and 13.0 μM, respectively), superior to those of honokiol (IC?? = 65.1, 62.0, 42.0, 75.0, and 55.4 μM, respectively). Importantly, compound 5c inhibited the migration and capillary-like tube formation of HUVECs in vitro.     

Free radical scavenging, antimicrobial and immunomodulatory activities of Orthosiphon stamineus

Orthosiphon stamineus is considered an important traditional folk medicine. In this study ethanol and aqueous extracts of O. stamineus were evaluated in vitro for their antioxidant, antimicrobial as well as for their immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). The DPPH radical scavenging method was used for the determination of antioxidant activity, while the antibacterial efficacy was investigated by both disc diffusion method and Minimum Inhibitory Concentration (MIC) against four bacterial strains (Gram-positive and Gram-negative). Furthermore, the immunomodulatory potential of the extracts was investigated through the MTT assay. Aqueous extract of O. stamineus exhibited significant free radical scavenging activity with IC?? 50 9.6 μg/mL, whereas the IC?? for the ethanol extract was 21.4 μg/mL. The best antimicrobial activity was shown by the aqueous extract of O. stamineus against Staphylococcus aureus, with inhibition zone of 10.5 mm and MIC value 1.56 mg/mL. Moreover, the results observed from the MTT assay showed that both plant extracts stimulated the PBMCs proliferation in vitro in a concentration-dependent manner, but the aqueous extract has remarkable activity against PBMCs. These findings indicate that O. stamineus showed high antioxidant activity and may be considered as an immunomodulatory agent.     

由2-羟基-1,4-萘醌合成2-乙氧基-1,4-萘醌

由2-羟基-1;4-萘醌合成2-乙氧基-1;4-萘醌;乙氧基萘醌; 羟基萘醌; 乙醇; 硝酸; 回流     

Studies on quinones. VIII. The application of michael adducts from 2-hydroxy-1,4-naphthoquinones for the preparation of dihydronaphthopyrandiones

Dihydronaphthopyran-5,10-diones 7,13, 16 and their corresponding dihydronaphthopyran-5,6-diones 8, 14,17 have been obtained starting from Michael adducts of 2-hydroxy- and 2-hydroxy-7-methoxy-1,4-naph-thoquinone ( 1, 9 ). An efficient synthesis of hydroxyhydrolapachol ( 4 ) employing 2-hydroxy-3-(3-oxobutyl)-1,4-naphthoquinone ( 5 ) is described.     

Synthesis of 3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin

The synthesis of an isomeric mixture of 4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl analogues 6 of the C-glycosylpyranonaphthoquinone antibiotic medermycin is described. The key 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 8 was prepared via Stille coupling of 6-(3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3-bromo-1,4- naphthoquinone 17 with (alpha-ethoxyvinyl)tributyl-stannane followed by hydrolysis and oxidation of the resultant hydroquinone 18. Bromonaphthoquinone 17 in turn was afforded by oxidative demethylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3- bromo-1,4,5-trimethoxynaphthalene 16 formed by regioselective bromination of 6-(4-acetyl-3-azido-2,3,6-trideoxy- beta-D-arabino-hexopyranosyl)-1,4,5-trimethoxynaphthalene 10. This latter naphthalene 10 was prepared via direct C-glycosylation of naphthol 12 with glycosyl donor 11 using BF3.Et2O in acetonitrile. The regioselectivity of the bromination of naphthalene 10 was independently determined by reductive monomethylation of the 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 22 to naphthol 23 followed by selective ortho bromination to bromide 24 and methylation to 16. Attempts to effect acetylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-3-bromo-1,4,5-trimethoxynaphthalene 16 and 3-bromo-6-(3-dimethylamino-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-1,4,5-trimethoxynaphthalene 26 via Stille coupling with (alpha-ethoxyvinyl)tributylstannane were low yielding thereby establishing the necessity to use an azido group as a latent dimethylamino group and a more electrophilic bromonaphthoquinone as the coupling partner for the Stille reaction. Addition of 2-trimethylsilyloxyfuran 9 to 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)- 5-methoxy-1,4-naphthoquinone 8 afforded the furofuran adducts 7 and 19 as an inseparable mixture of diastereomers. Oxidative rearrangement of this diastereomeric mixture using ceric ammonium nitrate afforded the inseparable diastereomeric furonaphthopyrans 6 and 20.     

Two New Syntheses of the Pyranojuglone Pigment α-Caryopterone

By a simple process, 3-methoxyjuglone (= 8-hydroxy-2-methoxy-1,4-naphthoquinone; 9 ) has been synthesized from 1,2,4-trimethoxybenzene ( 5 ) and converted, after prenylation, to α-caryopterone ( 1 ; Scheme 1), a pyranojuglone pigment from Caryopteris clandonensis. On the other hand, juglone (= 5-hydroxy-1,4-naphthoquinone; 12 ) was regioselectively prenylated at C(2) via its 1-methoxy-cyclohexa-1,3-diene adduct 15 (Scheme 2). The 2-prenyljuglone ( 4 ) thus formed led to 1 after oxidation and other reactions.     

两种含杂环的氨基萘醌化合物的合成

以2,3-二氯-1,4-萘醌为主要原料,分别与吗啡啉和糠胺在一定条件下反应生成2种含杂环的氨基萘醌类化合物。2,3-二氯-1,4-萘醌与吗啡啉及2,3-二氯-1,4-萘醌与糠胺物质的量比均为1∶2,反应温度为60℃,溶剂为乙醇。2,3-二氯-1,4-萘醌与吗啡啉反应时间为1 h,产物2-氯-3-吗啡啉基萘-1,4-二酮(a)收率为93.5%;2,3-二氯-1,4-萘醌与糠胺反应时间为4 h,产物N~2,N~3-二(2-呋喃甲基)-1,4-二((2-呋喃甲基)亚胺)-1,4-二氢化萘-2,3-二氯化铵(d)收率为46.7%。对产物进行IR、Uv、MS和H-NMR等分析表征。     

Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid molecule

To improve the anti-tumor effects of rhein and aloe-emodin, a rhein-aloe-emodin hybrid molecule (RH-AE) was synthesized from rhein and aloe-emodin in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Chemical and spectroscopic methods, such as 1H and 13C NMR spectroscopy, and HR-ESIMS were used for the structure identification of RH-AE. Using the cell counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared between RH-AE, rhein and aloe-emodin on human hepatoma HepG2, human nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK-OV-3, and human cervical cancer Hela cells. The results showed that the half inhibitory concentration (IC50) of RH-AE on HepG2, CNE, NCI-H460, SK-OV-3, and Hela cells were significantly lower than those of rhein and aloe-emodin. This showed that RH-AE has a better in vitro anti-tumor effect than rhein and aloe-emodin.     

Phytochemical analysis, cytotoxic activity and constituents-activity relationships of the leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae)

The leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae) have been refluxed successively with chloroform and alcohol to get chloroform extract and alcoholic extract. Both the extracts have been assayed for cytotoxicity against human colorectal tumour cells. The chloroform extract exhibited significant cytotoxicity with IC(50) 31?μg mL(-1) (p??200?μg mL(-1). The chloroform extract has been further proceeded for chemical analysis by GC-TOFMS and 178 components were identified including acids, amines, amides, aldehydes, alcohols, esters, benzene derivatives, bicyclic compounds, terpenes, hydrocarbons, naphthalene derivatives, furan derivatives, azulenes, etc. Nine components representing 51.73% of the total chloroform extract were detected as major components. Caryophyllene (14.41%) and Eicosanoic acid ethyl ester (12.17%) are the most prominent components of the chloroform extract. β-Caryophyllene (14.41%) as most abundant compound supports potent cytotoxicity as shown by chloroform extract.     

Synthesis,Crystal Structure and Biological Activity of 2-[(Pyridin-2-yl)methylthio]-1H-benzimidazole Derivatives

In order to discover the novel anti-tumor agents, a series of 2-[(pyridin-2-yl)methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[(3,4-Dimethoxypyridin-2-yl)methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828(16), b = 11.625(2), c = 13.463(2) ?, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.     

Control of charcoal rot fungus Macrophomina phaseolina by extracts of Datura metel

Methanolic leaf and fruit extracts of Datura metel were found highly effective in suppressing against Macrophomina phaseolina, the cause of charcoal rot disease. These extracts were further subjected to successive fractionation with n-hexane, chloroform, ethyl acetate and n-butanol. All the concentrations (3.125-200?mg?mL?1) of chloroform, ethyl acetate and n-butanol fractions of leaf extract, and n-hexane fraction of fruit extract completely inhibited the target fungal growth. Two compounds A and B from the n-hexane fraction of fruit extract and compound C from n-butanol fraction of leaf extract were obtained by TLC. Compound B exhibited the best antifungal activity with an MIC value of 7.81?μg?mL?1 that was at par with that of commercial fungicide mancozeb (80% w/w). This study concludes that M. phaseolina can be effectively controlled by natural antifungal compounds in n-hexane fraction of methanolic fruit extract of D. metel.     

Oxidation of 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (echinochrome A) by atmospheric oxygen 1. Structure of dehydroechinochrome

The nondestructive oxidation of 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone by atmospheric oxygen in the ground (triplet ³Σ_g^–) and excited (singlet ¹Δ_g) states in different solvents (acetone, dioxane, ethanol, aqueous ethanol, water) at room temperature involves the initial formation of 7-ethyl-5,6,8-trihydroxy-2,3-dioxo-2,3-dihydro-1,4-naphthoquinone (dehydroechinochrome) accompanied by the release of an H₂O₂ molecule into the reaction medium. Dehydroechinochrome, being highly susceptible to hydration, successively reacts with two H₂O molecules to form 7-ethyl-2,2,3,3,5,6,8-heptahydroxy-2,3-dihydro- 1,4-naphthoquinone as the relatively stable final product. In this form, it can be isolated from the mixture of reaction products.     

氮杂香豆雌酚衍生物的合成及其抗肿瘤活性

以间苯二甲醚为原料, 经碘代、偶联、胺解、分子内环化及脱甲醚环化共5步反应,合成9个氮杂香豆雌酚衍生物（6a~6i）, 其结构经¹H NMR, ¹³C NMR 和APCI-MS表征。采用MTT法研究了6对Hela、 SKOV3、 BEL-7404、 HepG2及A-549等癌细胞的体外生长抑制活性。结果表明：6h对SKOV3细胞的生长抑制活性最高,其IC₅₀值为81.58 μmol·L^-1。