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Withanolides are steroidal lactones commonly found in plants of the Solanaceae family that have significant medicinal value. In this study, three withanolides extracted from Iochroma arborescens leaves were isolated and characterized. These included withaphysalin F (3) and two newly identified epimeric compounds: 18 R - and 18 S - O -methyl-withaphysalin F (1 and 2). Their structures were elucidated by NMR, IR, MS, CD, and X-ray diffraction analysis, and their potential against cell proliferation and migration was investigated. The cytotoxic assay revealed activity against different tumor and non-tumor cell lines. (18 S)- O -methyl-withaphysalin F (2) presented cell death effects after at least 6 hours of exposure. MDA-MB-231 cells were exposed to 0.06 and 0.6 µM of (18 S)- O -methyl-withaphysalin F (2), and reductions in cell adhesion, migration, and clonogenicity were observed. Morphological analysis revealed negative regulation in filopodia, salience, and roughness, as well as alterations in cellular microarchitecture. These results provide clues as to the effects of (18 S)- O -methyl-withaphysalin F (2), allowing new molecular modifications to improve potency and selectivity and increase our antineoplastic arsenal. [ABSTRACT FROM AUTHOR]

• Ti–26Nb–1.2TiC composite is successfully developed via PM plus casting. • The composite exhibits clear partial superelasticity. • TiC particles effectively refine the grains of the shape memory composite (SMC). • The SMC shows much higher mechanical and corrosion properties compared to Ti–26Nb. • The SMC showed excellent cell viability in relation to MG-63 cells. Ti–Nb alloys have great potential in biomedical applications as bone-implant materials due to their low elastic modulus, superelasticity, high corrosion resistance, and good biocompatibility. However, the low yield strength and poor superelasticity of Ti–Nb alloys restrict their practical clinical applications. Here, we report the mechanical properties and superelasticity, corrosion behavior, and biocompatibility of a Ti–26 at.% Nb–1.2 vol.% TiC (Ti–26Nb–1.2TiC) shape memory composite (SMC) prepared by vacuum arc melting and hot rolling. The yield strength, critical stress for inducing martensitic transformation, and elongation of the Ti–26Nb–1.2TiC SMC and a Ti–26Nb alloy were 460 and 337 MPa, 251 and 115 MPa, and 27.2% and 24.1%, respectively. The recovery rate of the SMC under 4% pre-strain reached 91.4%, which was 1.2 times that of the Ti–26Nb. Electrochemical tests in Hanks' solution revealed that the corrosion current density, passive current density, and corrosion rate of the SMC were lower than those of the Ti–26Nb. Both the Ti–26Nb alloy and Ti–26Nb–1.2TiC SMC showed good cell viability with grade 0 cytotoxicity in relation to MG-63 osteosarcoma cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Five undescribed polyprenylated benzoylphloroglucinol derivatives (1 – 5), named garschomcinols A – E, and five known analogues (6 – 10) were isolated from the branches of Garcinia schomburgkiana. Their structures were determined on the basis of 1D and 2D NMR and HRESIMS analyses. The absolute configuration of the bicyclo [3.3.1]nonane core structure of the polyprenylated benzoylphloroglucinols was assigned by comparison of its experimental electronic circular dichroism data with that of related compounds. All isolated compounds were evaluated for their cytotoxicity in vitro against five cancer cell lines. Compound 6 showed potent cytotoxicity against five cancer cell lines including KB, HeLa S3, HT-29, MCF-7, and Hep G2 with IC50 values in the range of 5.05 – 7.03 µM. [ABSTRACT FROM AUTHOR]

Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C−D (1 − 2), together with two known congeners (3 − 4), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL-resistance-overcoming activity of 1 – 4 in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1 – 4 at 50 µ M with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1 – 4 alone. [ABSTRACT FROM AUTHOR]

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Two new maytansinoids, N -methyltreflorine (1) and methyltrewiasine (2), were isolated from the dried fruits of Trewia nudiflora , together with three known congeners (3 – 5). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 and 2 was determined by X-ray crystallographic analysis. Compounds 1 – 5 exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 – 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1 and 4 also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1 and 2 significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively. [ABSTRACT FROM AUTHOR]

Pyrethrum pulchrum is a rare Mongolian plant species that has been traditionally used as an ingredient in various remedies. Bioactivity-guided fractionation performed on the methanol extract of its aerial parts led to the isolation of 2 previously undescribed guaianolide-type sesquiterpene lactones, namely 1 β ,10 β -epoxy-8 α -hydroxyguaia-3,11(13)-dien-6,12-olide (1) and 1,8,10-trihydroxyguaia-3,11(13)-dien-6,12-olide (2), along with the isolation or chromatographic identification of 11 compounds, arglabin (3), 3 β -hydroxycostunolide (4), isocostic acid (5), (E)-9-(2-thienyl)-6-nonen-8-yn-3-ol (6), (Z)-9-(2-thienyl)-6-nonen-8-yn-3-ol (7), N 1 , N 5 , N 10 , N 14-tetra-p-coumaroyl spermine (8), chlorogenic acid (9), 3,5-di- O -caffeoylquinic acid (10), 3,5-di- O -caffeoylquinic acid methyl ester (11), 3,4-di- O -caffeoylquinic acid (12), and tryptophan (13). Their structures were assigned based on spectroscopic and spectrometric data. The antimicrobial, antiproliferative and cytotoxic activities of selected compounds were evaluated. The new compounds showed weak to moderate antimicrobial activity. Arglabin (3), the major sesquiterpene lactone found in the methanol extract of P. pulchrum , exhibited the highest activity against human cancer lines, while compound 1 also possesses significant antiproliferative activity against leukemia cells. [ABSTRACT FROM AUTHOR]

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp. , high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed. [ABSTRACT FROM AUTHOR]

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp. , high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed. [ABSTRACT FROM AUTHOR]

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp. , high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed. [ABSTRACT FROM AUTHOR]

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp. , high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed. [ABSTRACT FROM AUTHOR]

Haplophyllum tuberculatum is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, H. tuberculatum essential oils, hydrosols, the pure compounds R -(+)-limonene, S -(−)-limonene, and 1-octanol, as well as their combinations R -(+)-limonene/1-octanol and S -(−)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact. However, the combinations R -(+)-limonene/1-octanol and S -(−)-limonene/1-octanol showed less effect on HEp-2 cells than pure R -(+)-limonene and S -(−)-limonene after 24 h, 48 h, and 72 h. 1-octanol exhibited the highest concentration causing 50% cytotoxicity (CC50) on HEp-2 cells after 24 h (CC50 = 93 µg/mL) and 48 h (CC50 = 83 µg/mL). The antiviral assays showed that the tested samples exhibited potent inhibition of CV-B. IC50 values ranged from 0.66 µg/mL to 28.4 µg/mL. In addition, CV-B3 was more sensitive than CV-B4. Both CV-B strains are more inhibited when cells were pretreated with the plant compounds. The hydrosols have no effect, neither on HEp-2 cells nor on the virus. 1-octanol, S -(−), and R -(+)-limonene/1-octanol had important selectivity indexes over time. Although essential oils had potent antiviral activity, they can be considered for application in the pretreatment of cells. However, 1-octanol and the combinations are within the safety limits, and thus, they can be used as an active natural antiviral agent for CV-B3 and CV-B4 inhibition. [ABSTRACT FROM AUTHOR]

Haplophyllum tuberculatum is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, H. tuberculatum essential oils, hydrosols, the pure compounds R -(+)-limonene, S -(−)-limonene, and 1-octanol, as well as their combinations R -(+)-limonene/1-octanol and S -(−)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact. However, the combinations R -(+)-limonene/1-octanol and S -(−)-limonene/1-octanol showed less effect on HEp-2 cells than pure R -(+)-limonene and S -(−)-limonene after 24 h, 48 h, and 72 h. 1-octanol exhibited the highest concentration causing 50% cytotoxicity (CC50) on HEp-2 cells after 24 h (CC50 = 93 µg/mL) and 48 h (CC50 = 83 µg/mL). The antiviral assays showed that the tested samples exhibited potent inhibition of CV-B. IC50 values ranged from 0.66 µg/mL to 28.4 µg/mL. In addition, CV-B3 was more sensitive than CV-B4. Both CV-B strains are more inhibited when cells were pretreated with the plant compounds. The hydrosols have no effect, neither on HEp-2 cells nor on the virus. 1-octanol, S -(−), and R -(+)-limonene/1-octanol had important selectivity indexes over time. Although essential oils had potent antiviral activity, they can be considered for application in the pretreatment of cells. However, 1-octanol and the combinations are within the safety limits, and thus, they can be used as an active natural antiviral agent for CV-B3 and CV-B4 inhibition. [ABSTRACT FROM AUTHOR]

Three new pyrrolobenzoxazine sesquiterpenoids, talatrachyoxazines A – C (1 – 3), together with fourteen known compounds (4 – 17), were isolated from the fungus Talaromyces trachyspermus EU23. Their structures were identified by spectroscopic evidence and mass spectrometry. The absolute configurations of 1 – 3 were determined by NOESY data and comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 showed cytotoxic activity against HelaS3, KB, HT-29, MCF-7, and HepG2 cell lines with IC50 values of 7, 11, 10, 12, and 10 µM, respectively. Compounds 1 and 14 showed weak antibacterial activity against the gram-positive bacteria Bacillus cereus and Bacillus subtilis , while 1 – 3 and 14 showed weak antibacterial activity against the gram-negative bacterium Pseudomonas aeruginosa. In addition, compound 1 showed weak antibacterial activity against Escherichia coli. [ABSTRACT FROM AUTHOR]

Zinc (Zn) and its biocompatible and biodegradable alloys have substantial potential for use in orthopedic implants. Nevertheless, pure Zn with a hexagonal close-packed crystal structure has only two independent slip systems, therefore exhibiting extremely low elongation and yield strength in its as-cast condition, which restricts its clinical applications. In this study, as-cast Zn–xTi (titanium) (x = 0.05, 0.10, 0.20, and 0.30 wt.%) binary alloys were hot-rolled and their microstructures, mechanical properties, wear resistance, and cytocompatibility were comprehensively investigated for orthopedic implant applications. The microstructures of both as-cast and hot-rolled Zn–xTi alloys consisted of an α-Zn matrix phase and a TiZn 16 phase, while Zn–0.2Ti and Zn–0.3Ti exhibited a finer α-Zn phase due to the grain-refining effect of Ti. The hot-rolled Zn–0.2Ti alloy exhibited the highest yield strength (144.5 MPa), ultimate strength (218.7 MPa), and elongation (54.2%) among all the Zn–xTi alloys. The corrosion resistance of Zn–xTi alloys in Hanks' solution decreased with increasing addition of Ti, and the hot-rolled Zn–0.3Ti alloy exhibited the highest corrosion rates of 432 μm/y as measured by electrochemical testing and 57.9 μm/y as measured by immersion testing. The as-cast Zn–xTi alloys showed lower wear losses than their hot-rolled counterparts. The extracts of hot-rolled Zn–xTi alloys at concentrations of ≤ 25% showed no cytotoxicity to MG-63 osteosarcoma cells and the extracts of Zn–xTi alloys exhibited enhanced cytocompatibility with increasing Ti content. [ABSTRACT FROM AUTHOR]

Zinc (Zn) and its alloys have been proposed as biodegradable implant materials due to their unique combination of biodegradability, biocompatibility, and biofunctionality. However, the insufficient mechanical properties of pure Zn greatly limit its clinical application. Here, we report on the microstructure, mechanical properties, friction and wear behavior, corrosion and degradation properties, hemocompatibility, and cytocompatibility of Zn–3Cu and Zn–3Cu–0.2Ti alloys under three different conditions of as-cast (AC), hot-rolling (HR), and hot-rolling plus cold-rolling (HR + CR). The HR + CR Zn–3Cu–0.2Ti exhibited the best set of comprehensive properties among all the alloy samples, with yield strength of 211.0 MPa, ultimate strength of 271.1 MPa, and elongation of 72.1 %. Immersion tests of the Zn–3Cu and Zn–3Cu–0.2Ti alloys in Hanks' solution for 3 months indicated that the AC samples showed the lowest degradation rate, followed by the HR samples, and then the HR + CR samples, while the HR + CR Zn–3Cu exhibited the highest degradation rate of 23.9 μm/a. Friction and wear testing of the Zn–3Cu and Zn–3Cu–0.2Ti alloys in Hanks' solution indicated that the AC samples showed the highest wear resistance, followed by the HR samples, and then the HR + CR samples, while the AC Zn–3Cu–0.2Ti showed the highest wear resistance. The diluted extracts of HR + CR Zn–3Cu and Zn–3Cu–0.2Ti at a concentration of ≤25 % exhibited non-cytotoxicity. Furthermore, both the HR + CR Zn–3Cu and Zn–3Cu–0.2Ti exhibited effective antibacterial properties against S. aureus. [ABSTRACT FROM AUTHOR]

"Blue Amazon" is used to designate the Brazilian Economic Exclusive Zone, which covers an area comparable in size to that of its green counterpart. Indeed, Brazil flaunts a coastline spanning 8000 km through tropical and temperate regions and hosting part of the organisms accredited for the countryʼs megadiversity status. Still, biodiversity may be expressed at different scales of organization; besides species inventory, genetic characteristics of living beings and metabolic expression of their genes meet some of these other layers. These metabolites produced by terrestrial creatures traditionally and lately added to by those from marine organisms are recognized for their pharmaceutical value, since over 50% of small molecule-based medicines are related to natural products. Nonetheless, Brazil gives a modest contribution to the field of pharmacology and even less when considering marine pharmacology, which still lacks comprehensive in-depth assessments toward the bioactivity of marine compounds so far. Therefore, this review examined the last 40 years of Brazilian natural products research, focusing on molecules that evidenced anticancer potential–which represents ~ 15% of marine natural products isolated from Brazilian species. This review discusses the most promising compounds isolated from sponges, cnidarians, ascidians, and microbes in terms of their molecular targets and mechanisms of action. Wrapping up, the review delivers an outlook on the challenges that stand against developing groundbreaking natural products research in Brazil and on a means of surpassing these matters. [ABSTRACT FROM AUTHOR]

A phytochemical study of the methanol extract of the leaves of Embelia schimperi resulted in the isolation of three new alkenylresorcinols, 1 – 3 , together with the known analogs 4 – 7. Their structures were established by a combination of spectroscopic techniques. Compounds 1 – 7 exhibited moderate cytotoxic activity against human cervical cancer cells HeLa-S3 and more pronounced antimicrobial properties towards bacteria and filamentous fungi. The present study falls into an ongoing research project on the characterization of bioactive phenolic lipids from plants of the family Primulaceae. [ABSTRACT FROM AUTHOR]

Two new Δ12 ursene-type triterpenoid coumaroyl esters (1 and 2), one new Δ7,15 isopimarane-type diterpenoid glycoside (20), and two new irido- δ -lactone-type iridoids (21 and 22), together with 17 known pentacyclic triterpenoids (3 – 19), were isolated during the phytochemical investigation of a methanol extract of the whole plant of Vaccinium emarginatum. Their structures were determined by detailed analysis of standard spectroscopic data (MS, IR, 1D, and 2D NMR) and comparison with data of known analogs. The isolates were evaluated for their cytotoxicity against the PC-3 and Du145 prostate cancer cell lines (as assessed by an MTT cell proliferation assay), as well as for their anti-inflammatory activity via the inhibition of nitric oxide production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among the isolates, the triterpenoid coumaroyl and feruloyl esters (1, 3 , and 4) exhibited strong cytotoxicity against PC-3 prostate cancer cells, with 85.6 – 90.2% inhibition at 10.0 µg/mL. The pomolic acid coumaroyl and feruloyl esters (1 and 3) also showed moderate anti-inflammatory activity against nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells, with 59.2 (± 1.0) and 47.1% (± 0.2) inhibition at 12.5 µg/mL, respectively. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis (Tv) induces host cell damage through cysteine proteinases (CPs) modulated by iron. An immunoproteomic analysis showed that trichomoniasis patient sera recognize various CPs, also some of them are present in vaginal washes (VWs). Thus, the goal of this work was to determine whether TvCP2 is expressed during infection and to assess the effect of iron on TvCP2 expression, localization and contribution to in vitro cellular damage. Western-blotting (WB) assays using TvCP2r and vaginitis patient serum samples showed that 6/9 Tv (+) but none of the Tv (−) patient sera recognized TvCP2r. WB using an anti-TvCP2r antibody and VWs from the same patients showed that in all of the Tv (+) but none of the Tv (−) VWs, the anti-TvCP2r antibody detected a 27 kDa protein band that corresponded to the mature TvCP2, which was confirmed by mass spectrometry analysis. Iron decreased the amount of TvCP2 mRNA and the protein localized on the parasite surface and cytoplasmic vesicles concomitant with the cytotoxic effect of TvCP2 on HeLa cells. Parasites pretreated with the anti-TvCP2r antibody also showed reduced levels of cytotoxicity and apoptosis induction in HeLa cell monolayers. In conclusion, these results show that TvCP2 is expressed during trichomonal infection and plays an important role in the in vitro HeLa cell cytotoxic damage under iron-restricted conditions. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin, a flavonoid extracted from licorice root, has been shown to be active against most cancer cells; however, its antitumor activity is limited by its poor water solubility. The aim of this study was to develop a stable isoliquiritigenin nanosuspension for enhanced solubility and to evaluate its in vitro cytostatic activity in A549 cells. The nanosuspension of isoliquiritigenin was prepared through wet media milling with HPC SSL (hydroxypropyl cellulose-SSL) and PVP K30 (polyinylpyrrolidone-K30) as stabilizers, and the samples were then characterized according to particle size, zeta-potential, SEM (scanning electron microscopy), TEM (transmission electron microscopy), DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction), FTIR (Fourier transform infrared spectroscopy), XPS (X-ray photoelectron spectroscopy), and in vitro release. The isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 had particle sizes of 238.1 ± 4.9 nm and 354.1 ± 9.1 nm, respectively. Both nanosuspensions showed a surface charge of approximately − 20 mV and a lamelliform or ellipse shape. The dissolution of isoliquiritigenin from the 2 nanosuspensions was markedly higher than that of free isoliquiritigenin. In vitro studies on A549 cells indicated that the cytotoxicity and cellular uptake significantly improved after treatment with both nanosuspensions in comparison to the isoliquiritigenin solution. Furthermore, cell apoptosis analysis showed a 7.5 – 10-fold increase in the apoptosis rate induced by both nanosuspensions compared with pure drug. However, the cytotoxicity of pure drug and nanosuspension on normal cells (HELF) was lower, which indicated both isoliquiritigenin nanosuspensions have low toxicity to normal cells. Therefore, the isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 as stabilizers may be a promising approach to improve the solubility and cytostatic activity of isoliquiritigenin. [ABSTRACT FROM AUTHOR]

Ocotea fasciculata presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from Ocotea fasciculata , and (ii) an in vitro cytotoxicity study to estimate, for the first time, the LD50 values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium. The best condition for epimers isolation was achieved in normal-phase liquid chromatography. The lignan fraction (LF), previously obtained from the plant ethanolic extract, was purified yielding 17% and 29% of YAN and EPI-YAN, respectively. The in vitro study demonstrated that YAN and EPI-YAN were safe, and only at the highest concentration studied, a decrease on cell viability was observed. The estimated LD50 value was higher than 1612 mg/kg for both epimers. The LF, on the other hand, demonstrated an estimated LD50 of 422 mg/kg. Lignan cytotoxicity studies also evidenced that the higher cell viability was related to the higher concentration of fetal bovine serum as a source of albumin in medium. This is the first time the LD50 and safety of the isolated epimers were estimated, opening up great perspectives of success in in vivo studies. [ABSTRACT FROM AUTHOR]

The seeds of Nigella sativa var. hispidula are widely used in food preparation by the Uighur people in western China. Recently, series of oleanane triterpenoid saponins were extracted from the seeds of Nigella sativa var. hispidula , especially α -hederin as representative that exhibited strong antitumor activity. Compared to α -hederin, sapindoside B has just 1 more terminal xylopyranose in the 3-O position and displays similar effects against various human cancer cell lines with cisplatin. Considering this potential cytotoxic activity, a reliable LC-MS/MS method was developed to quantify sapindoside B in rat plasma, urine, and feces. Chromatographic separation was conducted on an Agilent Zorbax SB-Aq (3.0 × 150 mm, 3.5 µm) column via an isocratic elution procedure with acetonitrile and water containing 0.1% formic acid. Mass spectrometric detection was coupled with an electrospray ionization source in the MRM mode. The linear range of calibration curves was 15 ~ 3000 ng/mL in plasma/urine and 30 ~ 3000 ng/g in feces. The intra-day and inter-day precision was less than 11.1%, and accuracy ranged from 92.2% to 108.7%. The proposed method was validated and shown to be reliable, precise, and accurate and was successfully applied to its pharmacokinetics and excretion studies. Sapindoside B exhibited dosage-dependent pharmacokinetics in the range of 2.5 mg/kg to 12.5 mg/kg, and only about 2% of intravenous dose of sapindoside B was excreted by the feces and urine in its unchanged form over 48 h. These results provide further data support for evaluating the druggability of sapindoside B. [ABSTRACT FROM AUTHOR]

Four new barringtogenol C-type triterpenoid saponins, namely acerplatanosides A – D (1 – 4), along with 22 known compounds (5 – 26), were isolated from the stem bark of Norway maple (Acer platanoides). Their structures were elucidated on the basis of comprehensive spectroscopic analyses and chemical hydrolysis. This is the first report of triterpenoid saponins isolated from Norway maple. Compounds 1, 3 , and 4 showed cytotoxicity against 4 human cancer cell lines with IC50 values ranging from 9.4 to 39.5 µM. [ABSTRACT FROM AUTHOR]

Commiphora gileadensis , locally known as becham, is a plant used in traditional Arabian medicine for treating headache, constipation, stomach, joint pain, and inflammatory disorders. Several studies have reported its antibacterial properties; however, no study has demonstrated its antiviral activity. This study aimed to evaluate the antiviral activity of C. gileadensis as well as to isolate its active compound and investigate its mode of action. This activity was evaluated using 4 viruses, herpes simplex virus type 2 (HSV-2), respiratory syncytial virus type B (RSV-B), coxsackie virus B type 3, and adenovirus type 5 by performing the plaque reduction assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for enveloped and nonenveloped viruses, respectively. The methanol extract of C. gileadensis leaves only showed antiviral activity against enveloped viruses with a selectivity index of 11.19 and 10.25 for HSV-2 and RSV-B, respectively. The study of the mechanism underlying antiviral activity demonstrated a virucidal effect by direct contact with these target viruses. The active compound, isolated using bio-guided assays involving TLC, was identified as guggulsterone by HPLC-diode array detection coupled with electrospray ionization mass spectrometry. Guggulsterone is an antagonist of the bile acid receptor and a modulator of cholesterol metabolism; however, its antimicrobial properties have been reported for the first time in this study. [ABSTRACT FROM AUTHOR]

Recently, we introduced an epoxy group to mebendazole by a reaction with epichlorohydrin and obtained two isoforms, mebendazole C1 (M-C1) and mebendazole C2 (M-C2). The in vitro effects of mebendazole derivatives at different concentrations on Echinococcus multilocularis protoscoleces and metacestodes as well as cytotoxicity in rat hepatoma (RH) cells were examined. The results demonstrated that the solubility of the two derivatives was greatly improved compared to mebendazole. The mortality of protoscoleces in vitro reached to 70–80% after 7 days of exposure to mebendazole or M-C2, and M-C2 showed higher parasiticidal effects than mebendazole (P > 0.05). The parasiticidal effect of M-C1 was low, even at a concentration of 30 µ m. The percentage of damaged metacestodes that were treated with mebendazole and M-C2 in vitro at different concentrations were similar, and M-C1 exhibited insignificant effects on metacestodes. Significant morphological changes on protoscoleces and metacestodes were observed after treatment with mebendazole and M-C2. In addition, the introduction of an epoxy group to mebendazole also reduced its cytotoxicity in RH cells. Our results demonstrate that the introduction of an epoxy group not only improved the solubility of mebendazole, but also increased its parasiticidal effects on E. multilocularis and reduced its cytotoxicity in RH cells. [ABSTRACT FROM AUTHOR]

As part of our search for new cytotoxic and antimicrobial natural products from endolichenic fungi, 19 compounds including 1 new 10-member lactone (2), 1 new polyacetylene glycoside (3), 1 new brasilane-type sesquiterpenoid glycoside (4), and 2 isobenzofuran-1(3H)-one derivatives (5 and 6) were isolated from the solid culture of the endolichenic fungus Hypoxylon fuscum. Their structures were unambiguously elucidated by NMR spectroscopic data, MS, ECD (electronic circular dichroism) calculation, and chemical methods. The cytotoxic effects on K562, SW480, and HEPG2 cell lines and the antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli , and Candida albicans were assessed. Compounds 1, 2 , and 5 exhibited moderate cytotoxicity against K562, SW480, and HEPG2 cell lines while compounds 1, 9 , and 11 displayed weak antibacterial activity against S. aureus. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis induces cellular damage to the host cells (cytotoxicity) through the proteolytic activity of multiple proteinases of the cysteine type (CPs). Some CPs are modulated by environmental factors such as iron, zinc, polyamines, etc. Thus, the goal of this study was to assess the effect of glucose on T. vaginalis cytotoxicity, proteolytic activity and the particular role of TvCP2 (TVAG_057000) during cellular damage. Cytotoxicity assays showed that glucose-restriction (GR) promotes the highest HeLa cell monolayers destruction (~95%) by trichomonads compared to those grown under high glucose (~44%) condition. Zymography and Western blot using different primary antibodies showed that GR increased the proteolytic activity, amount and secretion of certain CPs, including TvCP2. We further characterized the effect of glucose on TvCP2. TvCP2 increases in GR, localized in vesicles close to the plasma membrane and on the surface of T. vaginalis. Furthermore, pretreatment of GR-trichomonads with an anti-TvCP2r polyclonal antibody specifically reduced the levels of cytotoxicity and apoptosis induction to HeLa cells in a concentration-dependent manner. In conclusion, our data show that GR, as a nutritional stress condition, promotes trichomonal cytotoxicity to the host cells, increases trichomonad proteolytic activity and amount of CPs, such as TvCP2 involved in cellular damage. [ABSTRACT FROM AUTHOR]

Four pairs of β -carboline enantiomers (1a / 1b – 4a / 4b), 2 β -carboline derivatives (5 – 6) with a single enantiomeric configuration, together with 2 known achiral congeners (7 – 8) were isolated from the stems of Picrasma quassioides. Their structures were elucidated on the basis of extensive spectroscopic analyses and quantum mechanical calculations. Compound 5 possesses a 4,5-seco β -carboline framework and represents the first example of this type of β -carboline alkaloids from nature. A possible biosynthetic pathway is proposed to generate the racemate 4 and the enantiomerically pure compounds 5 and 6. All isolates were screened for their cytotoxicity against hepatocellular carcinoma Hep3B and HepG2 cells, which revealed that enantiomeric compounds 4a and 4b had distinctive effects in HepG2 cells. Further investigation showed that 4b could induce apoptosis in HepG2 cells. [ABSTRACT FROM AUTHOR]

Three previously undescribed cardenolides, acovenosigenin A 3- O - α -L-acofriopyranoside (1), 14-anhydroacovenosigenin A 3- O -[ β -D-glucopyranosyl-(1″→4′)- O - α -L-acofriopyranoside] (2), and 14-anhydroacovenosigenin A 3- O -[ β -D-glucopyranosyl-(1″→4′)- O - α -L-acovenopyranoside] (3), together with the two already known ones, 14-anhydrodigitoxigenin 3- O - β -D-glucopyranoside (4) and acospectoside A (5), were isolated from the leaves of Acokanthera oblongifolia. The influence of cardenolides 1 – 3 and acovenoside A (found in the Acokanthera genus) on three cancer cell lines (HT29, HCT116, and AGS) was also investigated. The most promising results, in comparison with oxaliplatin, were obtained for compound 1 , which was found to be highly cytotoxic for all tested cell lines, HT29 (IC50 = 63.49 nM), HCT116 (IC50 = 67.35 nM), and AGS (IC50 = 80.92 nM). Unfortunately, 1 also showed similar toxicity towards normal lymphocytes (IC50 = 98.03 nM). [ABSTRACT FROM AUTHOR]

Chromatographic separation of extracts from the fungal biomass of a plant pathogenic fungus, Myrothecium roridum , yielded 8 trichothecene toxins including 6 type D trichothecenes (1 – 6) and 2 type A trichothecenes (7 – 8). 6′,12′-Epoxymyrotoxin A (1) and 7′-hydroxymytoxin B (2) were new macrocyclic trichothecenes, while the other trichothecenes were identified as myrotoxin B (3), myrotoxin D hydrate (4), 2′,3′-epoxymyrothecine A (5), miotoxin A (6), and 2 trichothecenes lacking the macrocyclic lactone system, roridin L-2 (7) and trichoverritone (8). The structures of these mycotoxins were characterized using spectroscopic methods. The absolute configurations of 1 and 2 were determined by NOESY and a comparison of their experimental and calculated ECD spectra. Most of these mycotoxins (1 – 4 and 6) exhibited highly potent antimalarial activity against Plasmodium falciparum. They also showed strong cytotoxicity towards KB and NCI-H187 cell lines (IC50 0.60 – 112.28 nM), as well as the Vero cell line (IC50 1.50 – 46.51 nM). [ABSTRACT FROM AUTHOR]

Two new arborinane-type triterpenes, myrotheols A (1) and B (2), two new arborinane-type glycosides, myrothesides C (3) and D (4), together with four known diterpenes (5 – 8) were isolated from the ethyl acetate extract of the endolichenic fungus Myrothecium inundatum. The structures of new compounds 1 – 4 were elucidated by NMR and MS analyses. The absolute configuration of 1 was assigned by a single-crystal X-ray diffraction experiment. Compounds 3 and 4 represent the first two natural 4-O-methyl- α -D-mannosides. Compounds 1 – 8 exhibited cytotoxicity against K562 and RKO human cancer cell lines. [ABSTRACT FROM AUTHOR]

A new cyclic pentapeptide, cotteslosin C (1), a new aflaquinolone, 22-epi-aflaquinolone B (3), and two new anthraquinones (9 and 10), along with thirty known compounds (2, 4 – 8, 11 – 34) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14), averufin (16), and sterigmatocyctin (19) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9 , and 10 was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18 – 21 , and 26 exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC50 values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32 , and 33 displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM. [ABSTRACT FROM AUTHOR]

Six new prenylated xanthones (1 – 6) and seventeen known xanthones were isolated from extracts of Garcinia bracteata leaves. Their structures were determined by extensive NMR and MS spectroscopic data analysis. The inhibitory activities of the isolates were assayed on HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines. Compounds 1 and 15 – 17 showed moderate inhibitory effects on tumor cell growth, with IC50 s ranging from 3.7 to 14.7 µM. [ABSTRACT FROM AUTHOR]

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum , exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro , human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer. [ABSTRACT FROM AUTHOR]

Galbanic acid is a natural sesquiterpene coumarin compound with different biological activities, particularly cytotoxicity against LNCaP (an androgen-dependent prostate cancer cell line). Galbanic acid induces apoptosis in LNCaP via down-regulation of androgen receptor. However, the poor water-solubility of galbanic acid limits further in vitro and in vivo studies. In this study we present the synthesis of galbanic acid-coated Fe3O4 magnetic nanoparticles and their cytotoxicity evaluation on three prostate cancer cell lines, including PC3 (an androgen-independent cell line), LNCaP, and DU145 (an androgen-independent cell line). The synthesized nanoparticles were characterized by X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, scattering electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering, and vibrating sample magnetometry. Our cytotoxicity evaluation demonstrated that galbanic acid was cytotoxic only against LNCaP cells, while the galbanic acid-coated Fe3O4 nanoparticles showed cytotoxicity on all tested cells, including androgen-dependent and -independent cell lines. This indicates that other mechanisms are involved in the cytotoxicity of galbanic acid in addition to androgen receptor down-regulation. In conclusion, the loading of galbanic acid on the surface of Fe3O4 magnetic nanoparticles turned out to be a successful approach to enhance the solubility and cytotoxicity of this compound.. [ABSTRACT FROM AUTHOR]

One new 15,16-seco-cycloartane triterpene (1), three new cycloartane triterpene glycosides (2-4), and five known compounds (5-9)wereisolatedfromtheaerialpartsof Actaea heracleifolia. The chemical structures of these compounds were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other spectroscopic methods. Selected compounds were evaluated for their cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in vitro. Compounds 3 and 4 showed weak activity against the HL-60, A-549, and MCF-7 cell lines with IC50 values ranging from 21.34 to 36.98 µM. [ABSTRACT FROM AUTHOR]

Cepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer. [ABSTRACT FROM AUTHOR]

Six new neo-clerodane diterpenoids (1-6), scutebatas X-Z, A1-C1, along with twelve known ones (7-18) were obtained via the phytochemical investigation of the aerial parts of Scutellaria barbata. Their structures were established by detailed spectroscopic analysis. The absolute configurations of 1 and 2, as the representative members of this type, were identified based on a circular dichroic exciton chirality method. Moreover, in vitro cytotoxicity of compounds 1-6 were evaluated against three human cancer cell lines (SGC-7901, MCF-7, and A-549) using the MTT method. Compound 6 showed cytotoxic activities against all the three cell lines with IC50 values of 17.9, 29.9, and 35.7 µM, respectively. [ABSTRACT FROM AUTHOR]

Three new bisindole alkaloids, 3'-(2-oxopropyl)-19,20-dihydrotabernamine (1), 3'-(2-oxopropyl)-ervahanine B (2), 19,20-dihydrovobparicine (3), and 20 known compounds were isolated from the aerial parts of Tabernaemontana bufalina. The structures of these alkaloids were elucidated using spectroscopic methods. The absolute configurations of 1-3 were determined by the circular dichroic exciton chirality method. Compounds 1-23 were screened for their cytotoxicity against two human cancer cell lines, A-549 and MCF-7. Ten compounds (1-3, 10, 14, 16, 17, 19, 22,and 23) exhibited inhibitory effects against the two human cancer cells with IC50 values of 1.19 ~ 6.13 µM. [ABSTRACT FROM AUTHOR]

The plants in the genus Derris have proven to be a rich source of rotenoids, of which cytotoxic effect against cancer cells seem to be pronounced. However, their effect on angiogenesis playing a crucial role in both cancer growth and metastasis has been seldom investigated. This study aimed at investigating the effect of the eight rotenoids (1-8) isolated fromDerris trifoliata stems on three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2) exhibited potent inhibition on both cell growth and migration of HCT116 colon cancer cells. Further, anti-angiogenic assay in an ex vivo model was carried out to determine the effect of the isolated rotenoids on angiogenesis. Results revealed that 12a-hydroxyrotenone (2) displayed the most potent suppression of microvessel sprouting. The in vitro assay on human umbilical vein endothelial cells was performed to determine whether compound 2 elicits anti-angiogenic effect and its effect was found to occur via suppression of endothelial cells proliferation and tube formation, but not endothelial cells migration. This study provides the first evidence that compound 2 could potently inhibit HCT116 cancer migration and anti-angiogenic activity, demonstrating that 2 might be a potential agent or a lead compound for cancer therapy. [ABSTRACT FROM AUTHOR]

Three diynes, octadec-17-ene-9,11-diynoate ethyl (1), 8-hydroxy-octadeca-13,17-diene-9,11-diynoate ethyl (2), and 8-hydroxy-octadec-13-ene-9,11-diynoate ethyl (3), were isolated from Ongokea gore seed oil. The structure assignment of these three compounds was based according to chemical and spectroscopic data. They were screened against Plasmodium falciparum, the parasite that causes malaria. In vitro microtest (Mark III, supported by the World Health Organization) was developed to assess the response of P. falciparum to the isolated three compounds, and statistical analysis were performed for determination of the concentration that inhibits 50% of the parasite maturation (IC50). Two of the three diynes (2 and 3) showed a very effective in vitro antimalarial activity with an IC50 of 4.5 and 1.7 µM, respectively. Compound 3 exhibited better activity than quinine (IC50 1.9 µM), the drug reference, while compound 1 had no antimalarial activity (IC50 > 125 µM). In the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity screening, all compounds showed no toxicity (mean IC50 of 90 µM for each compound). [ABSTRACT FROM AUTHOR]

The aerial parts of Guarea guidonia afforded three new tirucallane- type triterpenoids: 3,4-seco-tirucalla-4(28),8(9),24(25)- trien-7α,11α-dihydroxy-21,23-epoxy-3,11-olide, named guareolide (1), 3,4-seco-tirucalla-4(28),7(8),24(25)-trien-21-hydroxy- 21,23-epoxy-3-oic acid, named guareoic acid A (2), and 3,4-seco-tirucalla-4(28),7(8),24(25)-trien-21,23-epoxy- 3-oic acid, named guareoic acid B (3), of which 1 possessed an unusual seven-membered lactone ring. Seven known terpenes were also isolated and characterized as flindissone, 7- acetyldihydronomilin, picroquassin E, boscartol C, and cneorubins A, B, and X. Their structures were determined by spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance analysis and high-resolution mass spectrometry. The isolates were investigated for their potential cytotoxic activity on Jurkat, HeLa, and MCF7 cancer cell lines. Flindissone and compound 2 showed an antiproliferative activity in all cell lines. Further studies revealed that flindissone, the most active compound, induced in Jurkat and HeLa cells both cytostatic and cytotoxic responses. [ABSTRACT FROM AUTHOR]

The Hyacinthaceae family (sensu APGII), with approximately 900 species in around 70 genera, plays a significant role in traditional medicine in Africa as well as across Europe and the Middle and Far East. The dichloromethane extract of the bulbs of Massonia pustulata (Hyacinthaceae sensu APGII) yielded two known homoisoflavonoids, (R)-5-hydroxy-3-(4-hydroxybenzyl)- 7-methoxy-4-chromanone 1 and 5-hydroxy-3-(4-hydroxybenzyl)- 7-methoxy-4-chromone 2 and four spirocyclic nortriterpenoids, eucosterol 3, 28-hydroxyeucosterol 4 and two previously unreported triterpenoid derivatives, (17S, 23S)-17α,23-epoxy-3β,22β,29-trihydroxylanost-8-en-27,23- olide 5, and (17S, 23S)-17α,23-epoxy-28,29-dihydroxylanost- 8-en-3-on-27,23-olide 6. Compounds 1, 2, 3, and 5 were assessed for cytotoxicity against CaCo-2 cells using a neutral red uptake assay. Compounds 1, 2, and 5 reduced cell viability by 70% at concentrations of 30, 100, and 100 µM, respectively. Massonia bifolia yielded three known homoisoflavonoids, (R)-(4--hydroxy)-5-hydroxy-7-methoxy-4-chromanone 1, (R)- (4--hydroxy)-5,7-dihydroxy-4-chromanone 7 and (R)-(3'-hydroxy- 4--methoxy)-5,7-dihydroxy-4-chromanone 9, two previously unreported homoisoflavonoids, (E)-3-benzylidene- (3-,4'-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 8 and (R)-(3-,4'-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 10, and a spirocyclic nortriterpenoid, 15-deoxoeucosterol 11. Compounds 1, 1Ac, 7, 8, 9, and 10 were screened for antiangiogenic activity against human retinal microvascular endothelial cells. Some compounds showed dose-dependent antiproliferative activity and blocked endothelial tube formation, suggestive of antiangiogenic activity. [ABSTRACT FROM AUTHOR]

Three new angucycline glycosides, designated grincamycin I (1), J (2), and K (3), together with the known congener A- 7884 (4), were isolated from marine-derived actinomycete Streptomyces lusitanus SCSIO LR32. The structures of the new compounds were elucidated by comprehensive spectral data analysis. Compounds 2 and 4 exhibited antitumor activity against human cancer cells MDA-MB-435, MDA-MB-231, NCI-H460, HCT-116 and HepG2, and human normal breast epithelial cell MCF10A with IC50 values ranging from 0.4 to 6.9 µM. In addition, A-7884 (4) demonstrated antimicrobial activity against Micrococcus luteus with an MIC value of 1.95 µg/mL. [ABSTRACT FROM AUTHOR]

Five new flavones possessing a fully substituted A-ring with C- 6 and C-8 methyl groups, bougainvinones I--M (1-5), along with three known congeners, 2'-hydroxydemethoxymatteucinol (6), 5,7,3',4'-tetrahydroxy-3-methoxy-6,8-dimethylflavone (7) and 5,7,4'-trihydroxy-3-methoxy-6,8-dimethylflavone (8), were isolated from the EtOAc extract of the stem bark of Bougainvillea spectabilis. Their structures were established by means of spectroscopic data (ultraviolet, infrared, high-resolution electrospray ionization mass spectrometry, and one-dimensional and two-dimensional nuclear magnetic resonance) and single-crystal X-ray crystallographic analysis. The in vitro cytotoxicity of all isolated compounds against five cancer cell lines (KB, HeLa S-3, MCF-7, HT-29, and HepG2) was evaluated. Compound 5 showed promising cytotoxic activity against the KB and HeLa S-3 cell lines, with IC50 values of 7.44 and 6.68 µM. The other compounds exhibited moderate cytotoxicity against the KB cell line. [ABSTRACT FROM AUTHOR]

Terminalia sericea is a plant that has been used amongst others medicinally to treat wounds. The aim of this study was to assess the in vitro wound healing ability of T. sericea. Hot water, methanol, ethyl acetate, and hexane extracts were prepared. Thin layer chromatography (TLC) and ultra-performance liquid chromatography time of flight mass spectrometry (UPLC-TOF-MS) were used to determine the phytochemical classes and genus specific compounds present in the plant. Cytotoxicity was assessed in the SC-1 fibroblast and EA. hy926 endothelial hybrid cell lines using the sulforhodamine B assay. The effect of the extracts on cellular migration in both cell lines was assessed using the scratch assay. The major phytochemical classes detected in the extracts using TLC were alkaloids, coumarins, flavonoids, glycosides, phenolics, saponins, sterols, and terpenoids. The genus-specific compounds punicalagin, sericoside, anolignan B, and arjunic acid were identified in the extracts by means of UPLC-QTOF-MS. Cytotoxicity was not observed after 24 h of exposure and a generally low cytotoxic trend was noted after 72 h. A significant (p < 0.05) enhancement of cell migration in both cell lines was noted in the scratch assay. The wound healing ability of T. sericea is mainly attributed to the migratory and proliferative activity of the extracts responsible for the acceleration of wound closure. Isolation and individualized testing of the active compounds is warranted. [ABSTRACT FROM AUTHOR]

In a recent study, several new derivatives of antimycin A (AMA) were produced by means of a novel transacylation reaction, and these were shown to mediate selective toxicity toward cultured A549 human lung epithelial adenocarcinoma cells, as compared with WI-38 normal human lung fibroblasts. The purpose of our study was to investigate whether the analogues all expressed their cytotoxicity by the same mechanism. This was done by studying the effects of the compounds in several types of cell lines. In comparison with 2-Omethylantimycin, which acts at the locus of Bcl-2, none of the new derivatives exhibited a difference in cytotoxicity toward cells expressing different levels of Bcl-2. In cell lines that over- or underexpress estrogen or Her2 receptors, AMA analogue 2 exhibited Her2 receptor dependency at low concentration. Three compounds (1, 4, and 6) exhibited concentration-dependent increases in reactive oxygen species, with 6 being especially potent. Compounds 5 and 6 diminished mitochondrial membrane potential more potently than AMA, and 1 also displayed enhanced activity relative to 2-4. Interestingly, only 1 and AMA displayed strong inhibition of the respiratory chain, as measured by monitoring NADH (reduced nicotinamide adenine dinucleotide) oxidase. Because four of the analogues have positively charged substituents, two of these (4 and 6) were studied to see whether the observed effects were due to much higher level of accumulation within the mitochondria. Their presence in the mitochondria was not dramatically enhanced. Neither of the two presently characterized mechanisms of cell killing by AMA can fully account for the observed results. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) were previously isolated from the skin of the Ryukyu brown frog Rana okinavana. However, this species has recently been reclassified as two species, i.e., Rana kobai and Rana ulma. As a result, it was determined that AMPs isolated from R. okinavana were in fact products of R. kobai, but not of R. ulma. In the present study, we collected skin samples from the species R. ulma and cloned twelve cDNAs encoding AMP precursors for the acyclic brevinin-1ULa--1ULf, the temporin-ULa-ULc, ranatuerin-2ULa, japonicin-1ULa, and a novel peptide using reverse-transcription polymerase chain reaction techniques. The deduced amino acid sequence of the novel peptide had a high similarity to those of Rana chensinensis chensinin-1CEa--1CEc, which were cloned by Zhao et al. (2011), but had a low similarity with R. chensinensis chensinin-1, which was cloned by Shang et al. (2009). To avoid confusion with these two different chensinin-1 families, we termed our peptide ulmin-1. Among these peptides, we focused on two peptides, brevinin-1ULf and ulmin-1ULa, and examined the antimicrobial and cytotoxic activity of their synthetic replicates. In broth microdilution assays, growth inhibitory activities against Staphylococcus aureus, Bacillus cereus, and Candida albicans were detected for brevinin-1ULf but not for ulmin-1ULa, whereas scanning electron microscopic observations revealed that both peptides induce morphological abnormalities in these microbes. In addition, binding activity of ulmin-1ULa to the bacterial cell wall component lipoteichoic acid was higher than that of brevinin-1ULf. In contrast, hemolytic and cytotoxic activities of brevinin-1ULf were stronger than those of ulmin-1ULa. [ABSTRACT FROM AUTHOR]

Nine new and eleven known phorbol esters were isolated from an acetone extract of the seeds of Croton tiglium. Their structures were determined by extensive analysis of spectroscopic data. Eleven of these compounds were evaluated for their inhibition activity on human tumor cell lines HL-60 and lung carcinoma A549. 12-O-Tiglylphorbol-13-acetate (11), 12-O-(2-methyl)-butyrylphorbol-13-aetate (12), and 12-O-tiglylphorbol-13-isobutyrate (13) exhibited strong inhibition activity against both HL-60 and A549 cell lines with IC50 values ≤ 0.02 and ≤ 0.1 µg/mL, respectively. Compound 18 showed strong inhibition activity against the HL-60 cell line with an IC50 value of 0.02 µg/mL. [ABSTRACT FROM AUTHOR]