In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands

The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).     

Enhanced in vitro anticancer activity of quercetin mediated by functionalized CdTe QDs

We report in this study the effects of red-emitting CdTe QDs capped with cysteamine(Cys-CdTe) on the in vitro anticancer activity of the well-known flavenoid quercetin(Qu). Various techniques, including the methylthiazolyldiphenyl-tetrazolium bromide assay, the real-time cell electronic sensing system, the optical and fluorescence imaging, and electrochemical methods have been utilized to study the potential interactions of Cys-CdTe QDs with Qu. The observations demonstrate that the safe-dosage Cys-CdTe QDs can greatly improve the drug uptake and enhance the inhibition efficiency of Qu towards the proliferation of cancer cells such as HepG2 cells. This study implies that Cys-CdTe QDs may be used for cancer therapy and that they exert a synergic anticancer effect when bound to drug molecules.     

Repurposing homeopathic drug Lachesis 200C as an anticancer activity: In vitro and in ovo study

Cancer is one of the most critical health burdens with leading causes of death worldwide. Homeopathy is one of the complementary and alternative therapies, which utilizes venoms and toxins in ultra-high dilutions for therapeutics. In the present investigation, we used the homeopathy Lachesis 200C drug to study anticancer activity on the mouse fibroblast cells [L929], human prostate cancer cells [PC3], and in chick embryo model. Treating with Lachesis 200C showed 91.10% and 37.47% reduction in cell viability in L929 and PC3 respectively as compared to control by MTT assay. In the chick embryo model Lachesis 200C (dose of 50% and 100%) treatment resulted in antiangiogenic activity as compared to the control group. There was an antiproliferative and cytotoxic activity of Lachesis 200C in PC3 and L929 ​cell lines. Lachesis 200C inhibited the growth of PC3 cells. In the in vivo studies, Lachesis 200C treated chicks showed a significant decrease in or complete disappearance of blood vessels from chorioallantoic membrane (CAM) areas compared to control. The findings indicate that the level of angiogenesis was dramatically decreased by Lachesis 200C. Lachesis 200C showed the potential to act as an anticancer agent. Further studies with Lachesis200 could lead to a potential anticancer agent.     

In vitro study of proteins surface activity by tritium probe

A new technique for in vitro studies of biomacromolecules interactions, their adsorption at aqueous/organic liquid interfaces and distribution in the bulk of liquid/liquid systems was developed. The method includes (1) tritium labeling of biomolecules by tritium thermal activation method and (2) scintillation phase step with organic phase, which can be concerned as a model of cellular membrane. Two globular proteins lysozyme and human serum albumin tested. We have determined the conditions of tritium labeling when labeled by-products can be easy separated by means of dialysis and size-exclusion chromatography. Scintillation phase experiments were conducted for three types of organic liquids. Thus, the influences of the nature of organic phase on proteins adsorption and its distribution in the bulk of aqueous/organic liquid system were determined. It was found that proteins possess high surface activity at aqueous/organic liquid interface. Furthermore, values of hydrophobicity of globular proteins were found by the experiment.     

In vitro DNA scission activity of heterometallocenes

A comparative DNA scission activity study of azaferrocene, N-methyl-azaferrocene iodide and 3,3',4,4'-tetramethyl-1,1'-diphosphaferrocene (featuring iron in a +2 oxidation state), along with ferrocene (iron +2) and ferrocenium (iron +3) cation is described. Experiments indicate a high cleavage activity of azaferrocene and its N-methyl derivative in DMSO. DNA cleavage activity can be slowed down by addition of a free radical scavenger (thiourea) or triggered by addition of a reductive agent (dithiothreitol, DTT). The X-ray crystal structure of the N-methyl-2,5-dimethylazaferrocene cation (iron +2) with hexafluorophosphate as counter anion is also reported.     

In vitro anti-quorum sensing activity of phytol

Anti-quorum sensing activity of the diterpene phytol was evaluated in vitro for the first time. This compound (at three sub-MIC concentrations – 0.5, 0.25 and 0.125 MIC, respectively) reduced the formation of Pseudomonas aeruginosa PAO1 biofilm in the range of 74.00–84.33% exhibiting higher activity than the both positive controls used, streptomycin and ampicillin. Phytol (0.5 MIC) also effectively reduced P. aeruginosa twitching and flagella motility. Indeed, the bacteria treated were incapable of producing a twitching zone and had almost round, smooth and regular colony edges. Finally, the tested compound (0.5 MIC) exhibited good P. aeruginosa pyocyanin inhibitory activity (51.94%) practically to the same extent as streptomycin (52.09%). According to the experimental data obtained, this phytol property may inspire design of medical foods targeting P. aeruginosa quorum sensing activity.     

In silico identification of natural products with anticancer activity using a chemo-structural database of Brazilian biodiversity

Cancer is one of the leading causes of death worldwide, and the number of patients has only increased each year, despite the considerable efforts and investments in scientific research. Since natural products (NPs) may serve as suitable sources for drug development, the cytotoxicity against cancer cells of 2221 compounds from the Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBE_DB) was predicted using CDRUG algorithm. Molecular modeling, chemoinformatics, and chemometric tools were then used to analyze the structural and physicochemical properties of these compounds. We compared the positive NPs with FDA-approved anticancer drugs and predicted the molecular targets involved in the anticancer activity. In the present study, 46 families comprising potential anticancer compounds and at least 19 molecular targets involved in oncogenesis. To the best of our knowledge, this is the first large-scale study conducted to evaluate the potentiality of NPs sourced from Brazilian biodiversity as anticancer agents, using in silico approaches. Our results provided interesting insights about the mechanism of action of these compounds, and also suggested that their structural diversity may aid structure-based optimization strategies for developing novel drugs for cancer therapy.     

In vitro photodynamic activity of a series of methylene blue analogues

We have synthesized a series of symmetrical phenothiazines in which the methyl groups of methylene blue have been substituted by longer alkyl chains. Intrinsic photosensitizing ability was not altered by increasing the chain length. However, in vitro phototoxicity after 2 h incubation of RIF-1 murine fibrosarcoma cells followed the order n-propyl > n-pentyl > n-butyl > n-hexyl > ethyl > methyl, with ethyl and n-propyl analogues being 14- and 130-fold more phototoxic than methylene blue, respectively. All analogues also had an improved ratio of phototoxicity: dark toxicity (4:1 to 27:1) compared with methylene blue (3:1). Phototoxicity did not correlate with cellular phenothiazine levels, suggesting that the site of subcellular localization may be more important. After 2 h incubation of RIF-1 cells with the phototoxicity LD50 concentration, methylene blue and all analogues were observed to be localized in the lysosomes by fluorescence microscopy. On exposure to light, methylene blue relocalized to the nucleus, the ethyl analogue did not relocalize, whereas the more phototoxic n-propyl - n-hexyl analogues relocalized to the mitochondria. Relocalization to the mitochondria was associated with an octanol: buffer partition coefficient > or = 1. Therefore, the longer-chain analogues of methylene blue show significantly improved phototoxicity in vitro and, in addition, are expected to avoid the problems of mutagenicity associated with the nuclear localization of methylene blue.     

Astragalin identification in graviola pericarp indicates a possible participation in the anticancer activity of pericarp crude extracts: In vitro and in silico approaches

Graviola, soursop, or guanabana (Annona muricata L.), is an ethnomedical fruit consumed to alleviate headache, diarrhea, diabetes, and cancer. Pericarp is the inedible part of graviola least studied in comparison to seeds and leaves, even thought, it contains the highest concentration of graviola total polyphenols. Anticancer effect of graviola pericarp has been demonstrated in crude extracts attributing the effect to acetogenins, however, crude extracts contain several active molecules. Thus, the present work aimed to fractionate and purify an ethanolic crude extract from graviola pericarp. Purified graviola pericarp fraction (PGPF) was evaluated on cancerous and non-cancerous cell lines, and then was identified by NMR, TOF-MS, and HPLC. Finally, an in silico analysis was performed to predict targets cancer-related of the molecule detected. Our results revealed IC₅₀ values for cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), and non-cancerous cell line (HaCaT) of 92.85 ± 1.23, 81.70 ± 1.09, 84.28 ± 1.08, and 170.2 ± 1.12 µg PGPF/mL, respectively. In vitro therapeutic indexes estimated as quantitative relationship between safety and efficacy of PGPF were 1.83, 2.08, and 2.02 for HeLa, HepG2, and MDA-MB-231, respectively. The NMR analysis revealed astragalin (kaempferol-3-O-glucoside) in PGPF, a flavonoid not reported in graviola pericarp until now. Astragalin identity was confirmed by TOF-MS and HPLC. In silico results support previous reports about astragalin modulating proteins such as Bcl-2, CDK2, CDK4, MAPK and RAF1. Also, results suggest that astragalin may interact with other cancer-related proteins not associated previously with astragalin. In conclusion, astragalin may be contributing to the anticancer effect observed in graviola pericarp extracts.     

Synthesis and evaluation of in vitro anticancer activity of novel solasodine derivatives

<正>Solasodine 11 is a steroidal alkaloid with various biological activities.Herein,8 novel solasodine derivatives were synthesized and their effect on prostate cancer cell proliferation was assessed in vitro.Significant improvement in antiproliferative activity was achieved among some of the synthetic analogs.In particular,19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line(IC_(50) = 3.91μmol/L).     

Synergistic anticancer effects achieved by co-delivery of TRAIL and paclitaxel using cationic polymeric micelles

Cationic micellar nanoparticles self‐assembled from a biodegradable amphiphilic copolymer have been used to deliver human TRAIL and paclitaxel simultaneously. Polyplexes formed between paclitaxel‐loaded nanoparticles and TRAIL are stable with a size of ≈180 nm and a zeta potential at ≈75 mV. Anticancer effects and apoptotic pathway mechanisms of this drug‐and‐protein co‐delivery system are investigated in various human breast cancer cell lines with different TRAIL sensitivity. The co‐delivery nanoparticulate system induces synergistic anti‐cancer activities with limited toxicity in non‐cancerous cells. An advantage of this co‐delivery is a significantly higher anti‐cancer effect as compared to free drug and protein formulations.

     

Effect of extraction conditions of paprika oleoresins on their free radical scavenging and anticancer activity

Ground spice paprika was extracted with hexane, by conventional Soxhlet procedure (SX oleoresin), and with supercritical carbon dioxide at three different pressures — 20, 30 and 40 MPa (SF20, SF30 and SF40 oleoresins). The effect of extraction method and conditions on the colour intesity of paprika oleoresins, content of α-tocopherol, as well as antioxidant and antiproliferative activity was examined. Hexane showed highest selectivity for paprika pigments (886.02 ASTA), while α-tocopherol showed highest solubility (3846.9 mg kg^?1) in supercritical carbon dioxide at 20 MPa. All paprika oleoresins exhibited good superoxide anion radical scavenging activity SF30 being the best superoxide anion radical scavenger. Cell growth activity was evaluated in vitro in human cell lines:cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and colon adenocarcinoma (HT-29). The highest antiproliferative activity was exhibited by SX in MCF7 cell line (IC₅₀=14.28 mg mL^?1). Extract SF40 produced significant and selective antiproliferative action towards HeLa cell line. These results suggest that paprika oleoresins, due to high antiradical and tumor cell-inhibiting activity, can be regarded as functional food ingredients.      

In vitro antitumour activity of some organogermanium radioprotectors

Four germanium derivatives of 2,2′‐oxydiethanethiol and 2,2′‐thiodiethanethiol have been synthesized and characterized by ¹H and ¹³C NMR, mass spectroscopy and elemental analysis. The antitumour activity of one of them is comparable to those of cis‐platin and etoposide. Copyright © 2003 John Wiley & Sons, Ltd.     

In vitro solar protection factor,antioxidant activity,and stability of a topical formulation containing Benitaka grape (Vitis vinifera L.) peel extract

Abstract

A flavonoid enriched extract (FE) was obtained from grape peels, and in vitro SPF, antioxidant activity, and effects on cell viability of this extract were tested with the intent to develop a cosmetic product. A formulation was developed with the FE, and the stability of this mixture was evaluated in terms of pH, density, viscosity, and SPF (90-days). FE showed no cytotoxicity to human keratinocytes and an in vitro SPF of 18.56 (UV-spectrophotometry). Further, FE showed a UVA protection factor of 3.17?±?0.2, a critical wavelength of 318.0?±?0.1 and a UVA/UVB of 0.9. Antioxidant activity assays resulted in 92.08% and 86.85% of activity against DPPH and ABTS (IC₅₀ = 296.90?±?1.2?µg/mL and 643.13?±?0.9?µg/mL), respectively. Finally, SPF of formulation with FE was 12.45. Results from the in vitro SPF and product stability tests (especially storage under refrigeration), indicate that FE is a promising compound for use as an innovative sunscreen formulation.     

Synthesis,structures and in vitro anticancer activity of some germanium-substituted di-n-butyltin dipropionates

Organotin and organogermanium compounds are extensively studied for their wide range of biological activity. To link biological active properties of organotin and organogermanium, sixteen new germanium-substituted di-n-butyltin dipropionates with the form (R₃GeCHR¹CHR²COO)₂SnBu₂ⁿ·H₂O were synthesized.     

In vitro stabilization of acv synthetase activity fromStreptomyces clavuligerus

ACV synthetase (ACVS) fromStreptomyces clavuligerus is very labile. The study and in vitro application of this important enzyme for cephamycin biosynthesis requires a relatively stable preparation. The stability of the crude enzyme was substantially increased by dithio-threitol and the cofactor, magnesium (Mg²⁺). The purified enzyme was also unstable and especially sensitive to moderate to high temperature. Addition of the substrate L-valine (L-val) along with the cofactors (ATP and MG²⁺) raised the thermal inactivation temperature, and increased the stability of the enzyme at low temperature. Amino acids capable of replacing L-val as ACVS substrate generally stabilized the enzyme. The ACVS level remained high during fermentation in a complex medium containing high concentrations of amino acids, in contrast to the situation in chemically-defined medium.     

In vitro antitumor activity of triterpenes from Ceriops tagal

The embryo of Ceriops tagal was extracted with 95% ethanol at room temperature, and four triterpenes (1-4) were separated from this extract. For the first time these triterpenes were the separated from this plant. Compounds (1-4) were tested in vitro for antitumor activity against three cell lines (human liver cancer cell (H-7402), human B-lymphoblastoid cell (Raji), and human cervical carcinoma cell (Hela)). Compounds 1 and 3 were effective to inhibit cell proliferation and growth of H-7402 and Hela, the IC(50) of them on H-7402 were 14.42 microg mL(-1) and 9.97 microg mL(-1), and the IC(50) of them on Hela were 11.84 microg mL(-1) and 11.32 microg mL(-1). All compounds 1-4 were not effective to inhibit cell proliferation and growth of Raji. The effects of compound 4 on inhibiting proliferation and growth of these three cancer cells was also not obvious.     

In vitro evaluation of cytotoxic and mutagenic activity of avarol

The cytotoxicity of avarol, a main secondary metabolite of the Mediterranean sponge Dysidea avara, was in vitro screened by MTT assay against four human tumour cell lines. The colon HT-29 tumour cells practically showed to be the only sensitive ones towards this organic compound. No toxicity was found against the fetal lung fibroblast MRC-5 cells at the concentrations tested. In comparison with doxorubicin, used as a positive control, avarol actually exhibited at least 588-fold less toxicity towards normal MRC-5 cells. Finally, comet assay indicated that DNA fragmentation was almost fivefold higher upon the treatment with doxorubicin, compared to avarol. The obtained results have actually confirmed that avarol scaffold may contribute to development of new cytostatics inspired by nature.     

In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel.

Paclitaxel (Taxol), a diterpenoid isolated from Taxus brevifolia, is effective against several murine tumors, and is one of the most exciting anticancer molecules currently available. Due to its low solubility in water, it is clinically administered with polyethoxylated castor oil (Cremophor EL), which causes serious side effects. Inclusion of paclitaxel in solid lipid nanoparticles (SLNs) has proved to be a good approach to eliminate the need for Cremophor EL and improve the drug's antitumor efficacy. This paper describes the development of two types of long-circulating SLNs as colloidal carriers for paclitaxel. SLNs are constituted mainly of bioacceptable and biodegradable lipids. In vitro release kinetics showed that the release was very slow, the release of paclitaxel from F68-SLN is linear, and the release of paclitaxel from Brij78-SLN followed the Weibull equation. Pharmacokinetics was evaluated in KM mice after injection of paclitaxel formulated in Cremophor EL or in Brij78-SLN and F68-SLN. Encapsulation of paclitaxel in both SLNs produced marked differences compared with the free drug pharmacokinetics. F68-SLN and Brij78-SLN are long-circulating (t 1/2 beta, 10.06 and 4.88 h, respectively) compared with paclitaxel injection (t 1/2 beta, 1.36 h).