Normal Human Fibroblast Cells Research Articles

Selective Cytotoxic Effect of Dorycnium pentaphyllum Extract on Human Breast, Liver, and Lung Cancer Cells

Although some studies have evaluated the cytotoxic activity of different Fabaceae species, there has been only limited research into the cytotoxic effect of Dorycnium pentaphyllum. The purpose of this study was to determine the antioxidant properties and cytotoxic effect of D. pentaphyllum extract on various human cancer cells. The total phenolic content (TPC) of the extract was determined using colorimetric method. The cytotoxic effect of the extract on human lung (A549), liver (HepG2), and breast (MCF-7) cancer cells and a normal human fibroblast cells was assessed using the MTT assay. TPC value of extract was found as 140.3±1.1 mg gallic acid equivalent per g sample. Extract showed selective cytotoxicity on all studied cancer cells compared to normal fibroblast cells, and the IC50 values of the extract in the cancer cells range from 100.4 to 298.5 μg/mL. This is the first study to reveal the cytotoxic effect of D. pentaphyllum extract on cancer cell lines. Phytomedical applications of D. pentaphyllum may represent promising approaches in the treatment of cancer.

Facile design and spectroscopic characterization of novel bio-inspired Quercetin-conjugated tetrakis (dimethylsulfoxide)dichlororuthenium(II) complex for enhanced anticancer properties

A facile reflux approach was employed in the design of novel complexes using ruthenium(II) and quercetin for enhanced anticancer applications. The designed metal-based flavonoid complex was thoroughly characterized by employing powder XRD, 1H, 13C NMR, elemental analysis (C, H, N, S, O), FT-IR, XPS, and UV–Vis spectroscopy techniques. The cell toxicity and cell proliferation properties of the Quercetin-Ru(II) complex were investigated on the non-small cell lung cancer cell lines (A549) along with the lung normal cells (WI-38) and human dermal fibroblast (HDFa) cells. Significant cytotoxicity was observed with the newly designed complex on A549 cells at minimum concentrations of (10–30 µM). Interestingly, no remarkable cytotoxicity was observed in the WI-38 and HDFa cells. The same was confirmed by assessing cellular damage and nuclear damage via Atomic force microscopy (Bio-AFM) and Hoechst staining assay. Moreover, the results of intracellular reactive oxygen species (ROS) generation are also interesting to confirm the abilities of designed novel Quercetin-Ru(II) complex for anticancer applications.

Bis(imidazol-1-yl)methane-based heteroscorpionate metal(II) complexes: Theoretical, antimicrobial, antioxidant, in vitro cytotoxicity and c-Met tyrosine kinase studies

The C-centered bis(imidazol-1-yl)methane-based heteroscorpionate metal(II) complexes of the type [M(L1−3)Cl] (1–9), where M = Mn(II), Ni(II) or Cu(II) have been synthesized using the heteroscorpionate ligands, (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL1), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL2) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL3). The spectral and theoretical studies suggested tetrahedral geometry for manganese(II) and nickel(II) complexes, and square-planar geometry for copper(II) complexes. The antimicrobial activity of the complexes was evaluated against two Gram (–ve) (Shigella dysenteriae and Vibrio cholerae) and two Gram (+ve) (Bacillus cereus and Streptococcus faecalis) bacterial, and three fungal (Candida albicans, Candida glabrata and Candida krusei) strains. The antioxidant activity of the ligands and their nickel(II) and copper(II) complexes were determined by ABTS, DPPH and H2O2 free radical scavenging assays. In vitro cytotoxicity activity of the ligands and their nickel(II) and copper(II) complexes were tested against human breast adenocarcinoma (MCF-7), cervical (HeLa) and lung (A549) cancerous and normal human dermal fibroblast (NHDF) cell lines by MTT reduction assay. The copper(II) complex 8 exhibit higher cytotoxicity activity than the other complexes against all the tested cancer cell lines. Molecular docking studies of the complexes were also performed with c-Met tyrosine kinase receptor to determine the possible binding mode and predominant binding interactions.

Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles

Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the possibility of ELV mediating RIBE signals. We investigated whether ELV from 4 Gy irradiated mouse serum mediate RIBE signals. Induction of DNA damage was observed in cells that were treated with ICCM ELV and ELV from 4 Gy irradiated mouse serum. In addition, we treated CCCM ELV and ICCM ELV with RNases, DNases, and proteinases to determine which component of ELV is responsible for RIBE. Induction of DNA damage by ICCM ELV was not observed after treatment with DNases. After treatment, DNA damages were not induced in CCCM ELV or ICCM ELV from mitochondria depleted (ρ0) normal human fibroblast cells. Further, we found significant increase in mitochondrial DNA (mtDNA) in ICCM ELV and ELV from 4 Gy irradiated mouse serum. ELV carrying amplified mtDNA (ND1, ND5) induced DNA damage in treated cells. These data suggest that the secretion of mtDNA through exosomes is involved in mediating RIBE signals.

Theoretical, antimicrobial, antioxidant, in vitro cytotoxicity, and cyclin-dependent kinase 2 inhibitor studies of metal(II) complexes with bis(imidazol-1-yl)methane-based heteroscorpionate ligands

A series of C-centered heteroscorpionate-based homoleptic manganese(II), nickel(II), and copper(II) complexes of type [M(L1–3)2] (1–9) have been synthesized by using the ligands (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL1), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL2) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL3). The geometric parameters of the complexes were determined using UV-vis and theoretical studies suggesting distorted octahedral geometry around metal(II) ion. Frontier molecular orbital analysis supports bioefficacy of the complexes. Antimicrobial activity of the metal(II) complexes were determined against two Gram(–ve) (Escherichia coli and Klebsiella pneumoniae) and two Gram(+ve) (Bacillus cereus and Staphylococcus aureus) bacteria, and three fungal (Candida albicans, Candida glabrata, and Candida krusei) strains. Antioxidant activity of nickel(II) and copper(II) complexes were evaluated against ABTS, DPPH, and H2O2 free radicals. In vitro cytotoxicity activity of nickel(II) and copper(II) complexes against human breast adenocarcinoma (MCF-7), cervical (HeLa), and lung (A549) cancer cell lines along with one normal human dermal fibroblasts (NHDF) cell line were carried out by MTT assay, which shows the potent activity of copper(II) complex 8 with respect to the standard drug cisplatin. Molecular docking studies evidence the interaction of complexes with cyclin-dependent kinase 2 receptor (CDK2).

Synthesis and anti-tumor efficacy of novel 2, 4-diarylaminopyrimidine derivatives bearing N-(3-pyridinylmethyl) urea moiety as anaplastic lymphoma kinase inhibitors

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase responsible for development of various tumor types. In this study, we synthesized a series of novel 2,4-diarylaminopyrimidine derivatives possessing a unique N-(3-pyridinylmethyl)urea moiety as ALK inhibitors. The most promising analog 5m bearing a 3-methoxy-4-morpholinophenyl substituent significantly inhibited proliferation of ALK positive H3122 and Karpas-299 cells with IC50 values about 10 nM, which were comparable with positive control LDK378. Compound 5m suppressed phosphorylation of ALK and its downstream proteins, and showed low cytotoxicity on normal human primary fibroblast cells (BJ cells). The binding mode of 5m was proposed by docking simulation, which explains the important role of N-(3-pyridinylmethyl)urea moiety. Furthermore, compound 5m exhibited favorable liver microsomal stability and significant efficacy in H3122 xenograft mice model. Interestingly, compound 5m also showed broader anti-proliferative activity on other human tumor cell lines, which was different from other ALK inhibitors.

New homochiral and heterochiral Mo(VI) complex from racemic ligand: Synthesis, X-ray structure, diastereomers separation and biological activities

A diastereomeric pair (homochiral and heterochiral) of Schiff base dioxo molybdenum complex was synthesized using chiral ligand (HL: R/S-1-((naphtalen-3-yl)methylenamino)propan-2-ol) in racemic form. Then, to separation of this diastereomeric pair, crystallization method was proposed which was successful with acetonitrile. 1H NMR technique was used to confirm the results. The complexes thoroughly characterized using FT-IR, elemental analysis, 1H NMR and 13C NMR techniques, and MoO2L(LH2)1 has been structurally characterized using single-crystal X-ray diffraction. The cytotoxic activity of the new compounds has been evaluated using MCF-7 (human breast adenocarcinoma) and HeLa (human cervix adenocarcinoma), in addition to normal human fibroblast cells using the MTT cytotoxicity assay. Compounds MoO2L(LH2)1 and MoO2L(LH2)2 revealed IC50 values 18 µM and 37 µM on MCF-7 and 58 µM and 17 µM on HeLa, respectively. MoO2L(LH2)2 showed high selectivity (3–13 folds) for cancerous cells over normal cells, as the maximum cell mortality of 8.77%. Furthermore, The HSA- and DNA-binding of the Mo(VI) complexes were investigated by absorption, emission spectroscopy, viscosity measurements and molecular docking. Their binding constant are calculated as: HSA-binding of MoO2L(LH2)1 is 6.7 × 104 M−1 and of MoO2L(LH2)2 is 5.8 × 104 M−1, while their DNA-binding are 5.6 × 104 M−1 and 2.2 × 105 M−1, respectively. Their thermodynamic parameters were also determined at different temperatures.

Detection of Genomic Alterations Caused by Low-Dose Γ-Irradiation in Human Normal Fibroblast Cells

The effects of Low-Dose Radiation (LDR) on human health are still debated, despite LDR being ubiquitous in our environment, such as via radioactive substance leakage following an accident at a nuclear facility, as well as medical exposure for diagnosis and radiotherapy.

Bioactivities of Flavonoids from Lopezia racemosa.

Lopezia racemosa Cav. (Onagraceae) has been used in Mexican traditional medicine to alleviate stomachache, biliary colic, urine retention, stomach cancer, and skin, dental, buccal, and urinary infections. The objective of this study was to determine the bioactivities of specific parts of the plant to scientifically confirm its traditional use. Aerial parts and flowers were macerated and subsequently extracted with hexane, chloroform, and methanol. This study was focused on the analysis of polar components, and thus the methanolic fractions were selected for further investigations. These fractions were evaluated for their antimicrobial activity using a panel of bacterial Gram-positive and -negative strains, as well as fungal strains, including filamentous fungi and yeasts. In addition, the cytotoxic activity of the extract was assessed by MTT using the human-derived monocytic THP-1 and the normal human fibroblast cell lines. Various fractions showed antimicrobial activity against various pathogens, although the most relevant were against Pseudomonas aeruginosa and Trichophyton mentagrophytes. No inhibition of yeasts was recorded. Only four fractions showed cytotoxic effects when the human-derived THP-1 and fibroblast cells were assessed. The four flavonoids isolated from the extract were luteolin, luteolin-6-C-hexoside, luteolin-8-C-hexoside, and hyperoside. The biological activities presented in this study validate some traditional uses of the plant.

Synthesis and anticancer activity of 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine analogs and their phosphoramidates

A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (20–49) was synthesized by means of phosphorylation of 3′-[4-aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (7–11) with 4-chlorophenyl phosphoroditriazolide (14), followed by a reaction with the appropriate amine. The synthesized compounds 7–11 and 20–49 were evaluated along with four known anticancer compounds for their cytotoxic activity in human cancer cell lines: cervical (HeLa), nasopharyngeal (KB), breast (MCF-7), osteosarcoma (143B) (only selected compounds 20, 24, 28, 32–36, 38, 40, 46) and normal human dermal fibroblast cell line (HDF) using the sulforhodamine B (SRB) assay. Among 3′-[4-aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidines (7–11) the highest activity in all the investigated cancer cells was displayed by 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (9) (IC50 in the range of 2.58–3.61 μM) and its activity was higher than that of cytarabine. Among phosphoramidates 20–49 the highest activity was demonstrated by N-n-propyl phosphoramidate of 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (35) in all the cancer cells (IC50 in the range of 0.97–1.94 μM). Also N-ethyl phosphoramidate of 3′-[4-(3-fluorophenyl)-(1,2,3-triazol-1-yl)]-3′-deoxythymidine (33) exhibited good activity in all the used cell lines (IC50 in the range of 4.79–4.96 μM).

Anti-breast cancer potential of frullanolide from Grangea maderaspatana plant by inducing apoptosis.

Breast cancer is the leading cause of female mortality worldwide. Although there are several modern treatments for breast cancer, there is a high rate of recurrence for the majority of treatments; therefore, the search for effective anticancer agents continues. The present study aimed to investigate the anti-breast cancer potential of frullanolide, a compound which is isolated and purified from the Grangea maderaspatana plant, for selected human breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The MTT assay was used to assess cytotoxic activity in breast cancer cell lines of treatment with frullanolide at 1.25, 2.5, 5.0, 10.0 and 20.0 µg/ml. Additionally, the apoptotic induction ability of frullanolide at various concentrations [0.5×, 1× and 2× half maximal inhibitory concentration (IC50)] was investigated by flow cytometry and western blot analysis. Frullanolide exhibited strong anti-breast cancer activity against MDA-MB-468 (IC50, 8.04±2.69 µg/ml) and weak cytotoxicity against the MCF-7 (IC50, 10.74±0.86 µg/ml) and MDA-MB-231 (IC50, 12.36±0.31 µg/ml) cell lines. The IC50 of frullanolide was high in the human normal epithelial breast cell line (MCF-12A) and mouse fibroblast cell line (L-929). Density plot diagrams revealed that frullanolide induced apoptosis in MCF-7, MDA-MB-468 and MDA-MB-231 cells. Notably, a plausible anticancer mechanism was elucidated via cellular apoptosis by p53-independence in the treated MCF-7 cell line and p53-dependence in the treated MDA-MB-468 and MDA-MB-231 cell lines. In conclusion, the present study demonstrated that frullanolide may exert anticancer activity on breast cancer cell lines by inducing apoptosis. Frullanolide offers a possible novel approach to breast cancer therapy.

RNA-Seq analysis revealed genes associated with UV-induced cell necrosis through MAPK/TNF-α pathways in human dermal fibroblast cells as an inducer of premature photoaging

Exposing the skin to solar UV radiation induces cascades of signaling pathways and biological alterations such as redox imbalance, suppression of antioxidant genes and programmed cell death. Therefore, the aim of this study was to use RNA-Seq to unravel the effects of UV radiation on Normal Human Adult Fibroblast cells (NHDF). Cells were exposed to UV (20 mJ/cm2 for 3 mins) and incubated for 24 h. Total mRNA from the cells generated libraries of 72,080,648 and 40,750,939 raw reads from UV-treated and control cells respectively. Of the differentially expressed genes (DEGs) produced 2,007 were up-regulated and 2,791 were down-regulated (fold change ≥2, p < 0.05). The expression of 4 genes was validated with RT-qPCR. Chemokine signaling pathways in cancer were significantly activated and antioxidant genes were down-regulated. This study applied Next Generation Sequencing technology to reveal the genes and pathways involved in UV-induced human dermal fibroblast cells necrosis.

Natural dietary antioxidants containing flavonoids modulate keratinocytes physiology: In vitro tri-culture models

Ethnopharmacological relevanceSeveral traditional medicinal herbs are widely used for dermatologic and cosmetic preparations. The beneficial skin repair activity is detected in various phases of wound-healing process, such as cell-cell, cell-matrix interactions or collagen synthesis.Aim Of The Study: The study assessed the effects of Opuntia ficus-indica (L.) Mill. (Opuntia) and Milk Thistle (MT) (Silybum marianum (L.) Gaerth) on adult keratinocytes (HaCaT) functioning under basal condition or in the presence of mechanical damage (wounded cells). Materials and methodsThe role of the natural compounds was tested on HaCaT grown in mono-culture and tri-culture configurations. In tri-cultures models, HaCaT were treated with the conditioned media (CM) obtained by Human Normal Dermal Fibroblast (NHDF) and Human Dermal Microvascular Endothelial cells (HMVEC) co-cultures. Specifically, were tested cell viability, oxidative stress mechanisms (cytokines release and lipid peroxidation) and cellular remodelling (growth factors release or metalloproteinase modulation). Moreover, the migratory potential of HaCaT was analysed by the use of wound healing in vitro assay. ResultsOpuntia and MT differently modified the metabolism (EGF, MMP-9), and the migratory properties of HaCaT both under physiological conditions or upon mechanical damage (wounded cells). Moreover, both compounds modulated HaCaT response to oxidative stress. The response to the natural compounds were modified, and in some cases potentiated, in tri-culture configuration systems. ConclusionsThe data demonstrated that in vitro tri-culture approach is suitable to characterize the role of natural compounds on the complex communication between dermal-epidermal cellular components and microvascular endothelium. Specifically, Opuntia and MT are good alternatives to synthetic compounds in skin repair promotion.

ROS-responsive thioether-based nanocarriers for efficient pro-oxidant cancer therapy

A high level of intracellular reactive oxygen species (ROS) is one of the remarkable intrinsic features of cancer cells. Therefore, ROS-responsive drug carriers have received great attention for cancer-selective drug delivery. In this study, ROS-responsive thioether-bearing polymers (TEP) were synthesized for effective intracellular delivery of piperlongumine (PL) into cancer cells. PL is a pro-oxidant drug that induces cytotoxic oxidative stress in cancer cells. PL-loaded TEP nanoparticles (PL-TEP NPs) were successfully formulated by a nanoemulsion method. PL-TEP NPs showed ROS-sensitive disassembly, which leads to ROS-sensitive drug release. In addition, PL-TEP NPs showed higher cytotoxicity in human breast cancer cells (MCF-7) than in normal human dermal fibroblast cells (hDFB), demonstrating their cancer cell-specific pro-oxidant therapy. This study demonstrates that ROS-responsive TEP NPs are effective drug carriers for efficient intracellular delivery of hydrophobic drug, PL.

Transcriptomic analysis of human dermal fibroblast cells reveals potential mechanisms underlying the protective effects of visible red light against damage from ultraviolet B light

BackgroundUltraviolet B (UVB) radiation is a major cause of skin photodamage, including the damage associated with photodermatoses, aging, and cancer. Although many studies have shown that red light has photoprotective effects on skin, the mechanisms underlying these effects are still poorly understood. ObjectiveThe aim of this study was to identify the photoprotective effects of visible red light against UVB-induced skin damage in normal human dermal fibroblast cells using a transcriptomic approach. MethodsNext-generation sequencing-based transcriptomic analyses were used to profile transcriptomic alterations and identify genes that are differentially expressed by visible red light and by UVB exposure. To understand the biological networks among identified genes, a literature-based biological pathway analysis was performed. Quantitative real-time polymerase chain reaction assays were used for mRNA-level validation of selected key genes. ResultsWe observed that visible red light contributes to skin cell protection against UVB by modulating gene expression that enhances the adaptive response to redox and inflammatory balancing and by upregulating genes involved in DNA excision repair processes. We also identified that several key genes in the red light-induced biological network were differentially regulated. ConclusionsVisible red light enhanced the UVB-protective effects in normal human skin cells via the transcriptomic modulation of genes involved in cell-protective processes. Our findings from this next-generation sequencing analysis may lead to a better understanding of the cytoprotective effects of visible red light and provide direction for further molecular or mechanistic studies.

Synthesis, characterization and biological evaluation of novel antimony(III) iodide complexes with tetramethylthiourea and N-ethylthiourea

Novel trivalent antimony(III) complexes with tetramethylthiourea (TMTU) and N-ethylthiourea (NETU) were synthesized by the reaction of antimony(III) iodide (SbI3). Antimony(III) iodide complexes of formulae {[SbI2(µ2-I)(TMTU)2]2} (1) and {[(NETU)SbI2(µ2-I)2(µ2-S-NETU)SbI2(NETU)]} (2) were characterized by spectroscopic techniques (FT-IR, FT-Raman, 1H and 13C NMR), TG-DTA analysis and X-ray diffraction (XRD) analysis. Single-crystal X-ray diffraction studies showed that the complexes existed as doubly bridged (1) and triply bridged (2) dimers. Crystal structure of the ligand N-ethylthiourea was also determined with single crystal X-ray diffraction analysis.Complexes 1 and 2 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cells HeLa (cervix). The toxicity of 1 and 2 was evaluated on normal human fetal lung fibroblast cells (MRC-5). Both complexes showed selectivity against the cancerous, than normal cells. The influence of 1 and 2, on the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) was determined experimentally and theoretically. The complexes 1 and 2 exhibited higher activity than free ligands against LOX. The in vitro antibacterial activities of free ligands and their antimony(III) iodide complexes 1 and 2 were tested against two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) and two Gram-positive (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212) bacteria. The complexes 1 and 2 were much more effective in terms of antimicrobial activity compared to the free ligands.

Antibacterial, cytotoxicity and wound healing assessments of amine-functionalised zeolite Y

The antibacterial activities, cytotoxicity, and wound healing of amine(3-aminopropyltriethoxysilane (APTES))-functionalised zeolite Y against normal human fibroblast cells were studied. The characterisation of unmodified and amine-functionalised zeolites Y (Z, ZA 0.04, ZA 0.4, and ZA 0.6) by Fourier transform infrared spectroscopy, X-ray powder diffraction, and energy dispersive X-ray analysis proved that the APTES molecules were grafted onto the zeolite Y surface without distorting its framework structure. All amine-functionalised zeolite Y samples possessed antibacterial activities against several ATCC bacteria that were correlated with the increased amount of APTES on the zeolite Y surface. Conversely, when a higher concentration of APTES was grafted on the zeolite Y, higher cytotoxicity was observed against the fibroblast cells. Although the ZA 0.6 sample (zeolite Y functionalised with 0.6 M of APTES) had higher antibacterial activity, it was cytotoxic to the cells. Therefore, the selection of an antibacterial agent for human treatment purposes must also consider its cytotoxicity effect against human cells to ensure it is biocompatible.

Synthesis, characterization and cytotoxic activity of organoruthenium(II)-halido complexes with 5-chloro-1H-benzimidazole-2-carboxylic acid

Three new ruthenium(II)-arene halido complexes, [(η6-p-cymene) RuX(L)] (1–3), were synthesized in a reaction of [(η6-p-cymene)RuX2]2 with 5-chloro-1H-benzimidazole-2-carboxylic acid (HL) in ethanol (X– = Cl– (1), Br– (2), I– (3)). The complexes were characterized by elemental analysis, mass spectrometry, IR, 1H and 13C NMR spectroscopy. The cytotoxic activity of the ligand precursor and its ruthenium complexes was tested by MTT assay in human cancer cell lines: lung adenocarcinoma (A549), myelogenous leukemia (K562) as well as in one normal human fetal lung fibroblast cell line (MRC-5). The results show that ruthenium(II)-arene complexes possess enhanced cytotoxicity when compared to HL in the range of concentrations up to 300 µM. In terms of halido ligand substitution, cytotoxic activity toward A549 and K562 cell lines in 1–3 serie significantly increased (e.g., IC50 values for K562: 1: 205.76 µM; 2: 174.77 µM; 3: 83.97 µM). All studied compounds were found to be ineffective toward MRC-5. Hydrolysis of 1–3 was followed by UV-vis spectroscopy at 25 °C, revealing ligand-substitution reactions at the Ru(II) center. Compounds 2 and 3 underwent rapid hydrolysis ranging from a few minutes for the aquation to ca. 20 min, confirming typical Ru-arene behavior in aqueous solutions.

Preparation and characterization of hydroxyapatite incorporated silica aerogel and its effect on normal human dermal fibroblast cells

The development of biomedical materials is increasing nowadays due to the increasing demands in medical area and various manmade advanced materials have been explored. In this study, the hydroxyapatite (HA) which is widely used biomaterial has been incorporated in silica aerogel (SA) through sol-gel ambient pressure drying (APD) technique using amorphous silica from rice husk ash. The HA incorporated SA (HAESA) samples with different weight ratio of HA/SiO2 (0.05, 0.1, 0.5, 1.0 and 1.3) were characterized and studied for their in vitro biocompatibility against normal human fibroblast cells. Based on the characterization results from Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, energy dispersive X-ray analysis, transmission electron microscope and thermogravimetric analysis, the HAESA samples with lower weight ratio of HA/SiO2 (0.05, 0.1 and 0.5) were silica-rich materials compared to that of higher weight ratio (1.0 and 1.3) which were silica-deficient materials. This resulted in different effects towards in vitro cell viability where the silica-rich HAESA samples have higher biocompatibility compared to that of silica-deficient materials based on trypan blue and cell viability assays. The optimum weight ratio of HA/SiO2 was for HAESA-0.5 (weight ratio of 0.5) in which it has the characteristics of HA and SA, and this eventually resulted in the highest cell viability which is up to 180% after 48 h exposure. Therefore, it can be concluded that the right amount of HA incorporated in the SA network can be performed by using sol-gel APD technique and resulted in high biocompatibility which is suitable to be used as alternative biomaterial for soft tissue application.

Anticancer activity, dual prooxidant/antioxidant effect and apoptosis induction profile of new bichalcophene-5-carboxamidines

A series of thirteen new aryl/hetarylbichalcophene-5-carboxamidines was prepared and screened for an in vitro anti-proliferative activity against sixty cancer cell lines. The tested monocationic bichalcophenes displayed promising potent anticancer activity against most cancer cell lines with GI50 values of 1.34–3.09 μM. The most potent compound was derivative 8 (median GI50 and TGI values of 1.34 and 3.23 μM, respectively), being also the least cytotoxic in this bichalcophene series with an LC50 of 77.6 μM. The most responsive cancer cell lines were leukemia (SR and K-562) and colon (HCT-15 and HT29) with GI50 in the sub-micromolar range. The effect of the tested bichalcophenes on normal human lung fibroblast (WI-38) cell line showed that they exerted their antiproliferative activity outside the realms of causing any toxicity in normal cells. To study apoptotic profiles of representatives of this class, compounds 4h, 4i, and 8 were found to cause significant reductions in cdk1 expression in HCT-116 colon cells by 46, 79, and 84%, respectively versus 52% reduction by 5- Flourouracil (5-FU). These three compounds were also unique being the only derivatives that significantly elevated the expression of p53 by ∼2, 4, and 5 folds, respectively. The tested bichalcophenes exhibited moderate to potent antioxidant activity in DPPH and ABTS as well as hydroxyl radical scavenging assays. Moreover, compounds IIIb, IIIc, 4c, and 4i, showed the highest pro-oxidant activity. Finally, to aid future endeavors for optimization of this series, a 5 descriptor 2D-QSAR model was derived from the common physicochemical parameters of these bichalcophenes and the external validation proved the model's good predictive efficiency.