Dermal Fibroblast Cell Line Research Articles

Design, Synthesis, and Antimicrobial Evaluation of a New Series of N-Sulfonamide 2-Pyridones as Dual Inhibitors of DHPS and DHFR Enzymes.

Sulfonamides and trimethoprim (TMP) drugs are normally used to inhibit the action of dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes, respectively. In this work, a new series of N-sulfonamide 2-pyridone derivatives that combine the inhibitory activities of DHPS and DHFR into one molecule were synthesized and evaluated for its in vitro antimicrobial activity and the ability to inhibit the action of both enzymes simultaneously. The synthesis was carried out via the reaction of novel benzothiazol sulfonylhydrazide with ketene dithioacetal derivatives, and the structures of the resultant compounds were confirmed using spectral and elemental techniques. Among the synthesized compounds, five compounds 3b, 5a, 5b, 11a, and 11b were found to possess significant antimicrobial activities against tested bacterial and fungi strains. The compounds were also examined for their cytotoxicity on HFB4 human dermal fibroblast cell line using MTT assay. The in vitro enzyme assay study of these compounds against DHPS and DHFR enzymes showed that compound 11a was the most potent inhibitor against both enzymes with IC50 values of 2.76 and 0.20 μg/mL, respectively. Docking studies showed that this compound has occupied both the p-aminobenzoic acid and pterin binding pockets of DHPS as well as the pterin binding pocket of DHFR. The results of these investigations confirmed that compound 11a is the most potent dual DHPS/DHFR inhibitor.

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy.

Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2–oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.

Synthesis, Structural, and Cytotoxic Properties of New Water-Soluble Copper(II) Complexes based on 2,9-Dimethyl-1,10-Phenanthroline and Their One Derivative Containing 1,3,5-Triaza-7-Phosphaadamantane-7-Oxide.

A series of water-soluble copper(II) complexes based on 2,9-dimethyl-1,10-phenanthroline (dmphen) and mixed-ligands, containing PTA=O (1,3,5-triaza-7-phosphaadamantane-7-oxide) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Cu(NO3)(O-PTA=O)(dmphen)][PF6] (1), [Cu(Cl)(dmphen)2][PF6] (2), and neutral [Cu(NO3)2(dmphen)] (3). The solid-state structures of all complexes have been determined by single-crystal X-ray diffraction. Magnetic studies for the complex 1–3 indicated a very weak antiferromagnetic interaction between copper(II) ions in crystal lattice. Complexes were successfully evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and the antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa), colon (LoVo), and breast adenocarcinoma (MCF-7) cell lines. Complexes 1 and 3 revealed lower toxicity to NHDF than A549 and HeLa cells, meanwhile compound 2 appeared to be more toxic to NHDF cell line in comparison to all cancer lines. Additionally, interactions between the complexes and human apo-transferrin (apo-Tf) using fluorescence and circular dichroism (CD) spectroscopy were also investigated. All compounds interacted with apo-transferrin, causing same changes of the protein conformation. Electrostatic interactions dominate in the 1/2 – apo- Tf systems and hydrophobic and ionic interactions in the case of 3.

Synthesis and biological evaluation of some 4-aminoquinoline derivatives as potential antitubercular agents

BackgroundBased on bioisosteric similarities with thiacetazone, a series of 7-chloro-4-aminoquinoline derivatives have been designed and synthesized. The target compounds were elucidated by NMR, mass, and FTIR spectral data. All synthesized compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB), and human dermal fibroblast cell lines were used to assess toxicity of selected ligands.ResultsAll of the designed compounds showed inhibition of MTB with MIC of 1.56–50 μM. Among the tested compounds, 7c and 7g proved to be most potent MTB inhibitors (MIC = 1.56 μM).ConclusionsThe outcome of present study suggests that most of the synthesized compounds are sensitive to Mycobacterium tuberculosis and showed acceptable range for molecular parameters. Thus, 7-chloro-4-aminoquinolines could be a useful lead for the development of new MTB inhibitory agents.

Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis

BackgroundThere are different treatments for breast cancer and melanoma that mostly have some side effects. One of the therapeutic strategies is the use of natural components. Phenol components are a class of antioxidants in plants that have many biological functions like anticancer effects. Gallic acid (GA) is a natural polyhydroxy phenolic compound and commonly found in various foods. In the present study, GA effects alone and in combination with low-level laser irradiation on human dermal fibroblast cell line (HDF), human non-tumorigenic breast epithelial cell line (MCF10A), breast cancer cell line (MDA-MB-231) and melanoma cancer cell line (A375) was under the investigation.MethodsThe normal and cancerous cell lines were exposed to 660 nm low-level laser with 3 J/cm2 for 90 s. Then, the cells were treated with different concentrations of GA for 24 h. In another study, the cell lines firstly were treated with GA and then exposed to low-level laser irradiation. The effects of GA and low-level laser on cell survival and apoptosis were examined using MTT assay, light microscopy, ROS production assay, fluorescence microscopy (AO/EB double staining) and flow cytometry.ResultsThe results showed that pre-treatment with low-level laser and then GA reduced the survival of breast cancer cells and melanoma more than the first treatment with GA and then low-level laser irradiation. Our findings showed that ROS production in cells treated with both low-level laser and GA was more than the cells treated with GA alone. The apoptosis and ferroptosis assays confirmed the MTT results which combination treatment with low-level laser and then GA increase the cell death probably via apoptosis and ferroptosis cell death mechanisms compared to GA alone.ConclusionsThis study suggests that low-level laser irradiation alone is not able to cause death in human normal and cancerous cells. Preirradiation followed by GA treatment did not change the cell viability in human normal significantly but reduces the cell survival of cancer cells more than GA alone.

Aluminium and calcium lake pigments of Lac natural dye

This work presents the physicochemical properties of the prepared lac lakes. The study revealed the stability, cytotoxicity and use of lac lake pigment as a cosmetic colorant. SEM, XRD and DSC were used to study the characteristics of the lac lakes.. The color stability of lac dye and its lakes was investigated at ambient temperature and at 45 °C, in sunlight,fluorescent light and darkness, for 3 months. Cytotoxicity on human dermal skin fibroblast cell lines was tested using MTT assay and the use of the lakes as a colorant in lip color product was studied. Different metal salts resulted in lac lakes of different shades and appearance. SEM, XRD and DSC results indicated that the morphology and structure of lac dye were changed after reacting with metal salts which support the coordination of metal ion with lac dye. The lac lakes were not cytotoxic to human dermal skin fibroblast cells (0.78-100 µg/mL). Lac lakes exhibited less alteration of color shade over acidic and basic conditions when compared with the lac dye itself. Additionally, the lake pigments displayed better color stability than lac dye and produced an orange-brown shade of lip color product. The results suggest that lac lake pigments have good potential for use as cosmetic colorant.

Electrospinning 3D bioactive glasses for wound healing

An electrospinning technique was used to produce three-dimensional (3D) bioactive glass fibrous scaffolds, in the SiO2–CaO sol-gel system, for wound healing applications. Previously, it was thought that 3D cotton wool-like structures could only be produced from sol-gel when the sol contained calcium nitrate, implying that the Ca2+ and its electronic charge had a significant effect on the structure produced. Here, fibres with a 3D appearance were also electrospun from compositions containing only silica. A polymer binding agent was added to inorganic sol-gel solutions, enabling electrospinning prior to bioactive glass network formation and the polymer was removed by calcination. While the addition of Ca2+ contributes to the 3D morphology, here we show that other factors, such as relative humidity, play an important role in producing the 3D cotton-wool-like macrostructure of the fibres. A human dermal fibroblast cell line (CD-18CO) was exposed to dissolution products of the samples. Cell proliferation and metabolic activity tests were carried out and a VEGF ELISA showed a significant increase in VEGF production in cells exposed to the bioactive glass samples compared to control in DMEM. A novel SiO2–CaO nanofibrous scaffold was created that showed tailorable physical and dissolution properties, the control and composition of these release products are important for directing desirable wound healing interactions.

Enhanced topical econazole antifungal efficacy by amine-functionalized silica nanoparticles

The present study aims at developing efficient econazole (ECO) platforms as topical creams for the treatment of fungal skin infections. The hexagonal mesoporous silica nanoparticle, known as MCM41, was synthesized and functionalized by aminopropyl groups (MCM41- $$\hbox {NH}_{2})$$ . Various ECO concentrations were loaded into MCM41 and MCM41- $$\hbox {NH}_{{2}}$$ (MSNs); the optimized complexes with the highest entrapment efficiencies were characterized by X-ray powder diffraction, scanning electron microscopy (SEM) and gas-volumetric analysis (BET). SEM images showed a spherical shape of the parent nanoparticles—higher drug loading and incorporation into the nanoparticles were obtained by amino-functionalized MCM41. Cytotoxicity assays of MCM41 and MCM41- $$\hbox {NH}_{{2}}$$ and the ECO inclusion complexes elucidated no toxicity to human dermal fibroblast cell lines. Enhanced antifungal activity against Candida albicans was observed for ECO/MCM41- $$\hbox {NH}_{{2}}$$ compared with ECO/MCM41 and simple cream. No irritation was observed by the cream containing ECO/MSN application on white male rabbit skin after 72 h. MSNs were stable within 1 year storage. ECO-loaded silica nanoparticles can be considered for the development of reliable alternatives to ECO cream for the treatment of skin fungal infections.

Design, synthesis, and in vitro evaluation of novel 1,3,4-oxadiazolecarbamothioate derivatives of Rivastigmine as selective inhibitors of BuChE

Rivastigmine has been prescribed for the therapy of Alzheimer’s disease (AD) symptoms. This drug is classified in the carbamate derivative group that has dual activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). According to the structure of Rivastigmine and its performance, a new series of 5-aryl-1,3,4-oxadiazole-2-carbamothioate compounds I–XI was synthesized using structure-based drug discovery approaches. For this purpose a set of these compounds were designed with computational docking method and their interactions with amino acid residues in the active sites of AChE and BuChE checked out. The structures of synthesized compounds were established by physicochemical and spectroscopic methods. The carbamoyl moiety of Rivastigmine structure was modified to carbamothioate and the effects of 1,3,4-oxadiazole heterocycle as a pharmacophoric nucleus were investigated. The potential of the synthesized compounds I–XI was evaluated against two most known agents of AD (AChE and BuChE) to determine their IC50 values. The results of the docking showed the range of binding affinity for the best poses of ten individual conformers for any compounds (I–XI) was between −7.81 (VI) and −6.75 (II) kcal/mol. The results of biological experiments displayed that most synthetic compounds (I–VIII) showed moderate to excellent selective activity range against BuChE (0.51–69.44 µM). In vitro cytotoxicity evaluation of these compounds (I–XI) by MTT assay on human dermal fibroblast (HDF) cell line exhibited no activity against HDF. The compound VI [S-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl) ethyl(methyl)carbamothioate] showed the most stable binding affinity (−7.81 kcal/mol) and the lowest IC50 value (0.51 µM) in comparison with Rivastigmine with 7.72 µM and Donepezil with 5.20 µM against BuChE.

Action mechanism of anti-wrinkle effect of Rhamnus yoshinoi methanol extract in human dermal fibroblast and keratinocyte cell lines.

Rhamnus yoshinoi is a deciduous broad-leaf bush and endemic species widely found in Korea. Recently, we reported that R. yoshinoi methanol extract (RYME) had excellent antioxidant activity and inhibition of collagenase and elastase activity in cell-free system. In this study, we investigated the ability of RYME to control the mRNA and protein expression levels of the known skin wrinkle-related factors in cultured human dermal fibroblast and keratinocyte cell lines. Treatment with 100 or 200μg/mL RYME strongly blocked the UVB-induced downregulation of type 1 collagen mRNA expression (p < 0.001) and partially blocked the UVB-induced upregulation of MMP-3 mRNA expression in HaCaT human keratinocytes (p < 0.05 or p < 0.001). Treatment with RYME at 100μg/mL considerably decreased MMP-1 mRNA expression in UVB-exposed HaCaT cells (p < 0.01). In HaCaT cells, RYME exhibited the potential to improve UV light-induced skin wrinkles. Moreover, RYME selectively inhibited the UVB-induced ERK-1/2 protein phosphorylation in CCD-986sk human dermal fibroblasts at 80 and 160μg/mL. UV-induced ERK-1/2 protein phosphorylation is one of the major mechanisms of the generation of UV-induced skin wrinkles. Therefore, it is likely that the anti-skin wrinkling effect of RYME could be attributable to selective inhibition of UV induced ERK-1/2 protein phosphorylation.

P53(Cp44), an Endogenous Human p53 Fragment Generated via M-Calpain-Mediated Cleavage Beyond Degradation

Endogenous fragments of p53 identified recently in human cytomegalovirus (HCMV)-infected human lung fibroblasts, specifically a ~44-kDa N- terminal fragment referred to as p53(Cp44), have been shown to be generated via m-calpain cleavage. p53(Cp44) appeared to be tightly associated with a chromatin-rich fraction, and was stabilized by the proteasome inhibitor MG132, particularly in mock-infected cells. The N- terminal p53 fragments were also present in three human dermal fibroblast cell lines tested, including fibroblasts isolated from post-burn hypertrophic scar. Understanding the biological functions of these fragments in the regulation of physiological and pathological processes, and the mechanisms regulating their generation and degradation, may shed light on currently unrecognized aspects of p53 regulation and function, and may provide a pathway for drug discovery.

Designing biocompatible and multicolor fluorescent hydroxyapatite nanoparticles for cell-imaging applications

In recent years, there has been a growing effort toward the synthesis, engineering and property tuning of biocompatible nanoparticles (NPs) that can be detected by confocal microscopy and then used as fluorescent probes. Defect-related fluorescent hydroxyapatite (HA) is attracting considerable attention as a suitable material for cell-imaging owing to its excellent biocompatibility, biodegradability, easy cell internalization capability, and its stable and intense blue fluorescence. Although the self-activated fluorescence of HA is advantageous, as it avoids the use of lanthanide dopants, organic dyes, or the need to be combined with other fluorescent inorganic nanocrystals, its preparation by simple procedures with fine control of the defects which govern this property remains challenging. In this study, we propose a new, simple, and cost-effective strategy of fluorescence imaging using HA nanorods (HAnrs) obtained by chemical precipitation followed by heat treatment at relative low temperature (350°C) without using any sophisticated equipment or inorganic/organic additives. Structural, compositional, and morphological analysis, as well as a cytotoxicity assay, are described in detail. The fluorescence characterization of HAnrs shows an intense bluish-white broad-band emission (λmax = 535 nm), and the defects which cause this behavior are studied by temperature-dependent photoluminescence measurements (38–300 K). Moreover, the high density of defects in heat-treated HA leads to tunable fluorescent property (λmax = 399–650 nm) across the entire visible spectrum as a function of the excitation wavelength (λexc = 330–630 nm) with the potential for further multicolor imaging applications. Labeling results by confocal microscopy show that HAnr co-cultured with human dermal fibroblast cell line exhibit fluorescence signals in the cells even after 48 h of incubation with no evident cytotoxic effects. Therefore, heat-treated fluorescent HAnr can be utilized for tracking and monitoring cells and is a safe alternative for the traditional probes used in bioimaging procedures.

Evaluation of biological and cytocompatible properties in nano silver-clay based polyethylene nanocomposites

Nano-toxicological evaluation of a biomaterial is of primordial importance for application in therapeutics. This is one of first reports on systematic analysis of in vitro and in vivo cytocompatible properties of an antimicrobial polyethylene/silver-clay hybrid nanocomposite. The polymeric nanocomposite has been prepared using melt compounding route by a twin screw extruder with silver-clay hybrid content varying from 1 to 5 wt%. The morphology of the polyethylene/silver-clay nanocomposites was investigated using a combination of TEM and XRD techniques. The antimicrobial studies suggest strong biocidal action against E. coli, S. aureus and A. niger. In vitro cytocompatibility studies show excellent compatibility with human erythrocytes and dermal fibroblast cell lines, as compared to powder form silver-clay hybrids which demonstrated mild toxicity. Histopathological analysis of skin tissues excised from rats surgically stitched with nanocomposite film show no morphological change following 21 days of exposure. The developed nanocomposites show excellent antimicrobial activity coupled with cytocompatibility and are hence potential candidates for biomedical applications.

Synthesis and in vitro anticancer activity of new gemcitabine-nucleoside analogue dimers containing methyltriazole or ester-methyltriazole linker.

Two series of novel gemcitabine-nucleoside analogue dimers were synthesized using the 'click' chemistry approach. In the first series of dimers (21-30), the nucleoside units were connected with a stable methyltriazole 4N-3'(or 5')C linker whereas in the second series (31-40) with a cleavable ester-methyltriazole 4N-3'(or 5')C linker. Dimers 21-40 were evaluated for their cytotoxic activity in five human cancer cell lines such as cervical (HeLa), nasopharyngeal (KB), lung (A549), brain (U87), liver (HepG2) and normal dermal fibroblast cell line (HDF) using the sulforhodamine B (SRB) assay. Compound 29 comprising two gemcitabine (dFdC) units exhibited the highest activity among dimers 21-30. The activity of compound 29 was higher than that of dFdC in all the studied cancer cell lines. A similar order of activity was observed for compounds 25, 28, and 30. The best activity among all the dimers synthesized was displayed by compound 39, comprising two gemcitabine units with a cleavable linker. The activity of compound 39 was 5 to 9 times higher than that of dFdC, depending on the cell line. In addition, marked cytotoxic activity was shown by compounds 31, 36, 38, and 40.

Synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery, and theranostic applications

Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into the active site without any side effects. Herein, ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl) bis (2-methoxy-4,1-phenylene) diacetate acetyl curcumin (AC)-loaded poly(lactic-co-glycolic acid) (PLGA) core/shell liposome nanoparticles (ACPCSLNPs) were prepared using an electron spray method under an applied electric field, which facilitated the uniform formation of nano-sized liposome nanoparticles (LNPs). Then, kinetically controlled and sustained drug release profiles were investigated using the as-prepared ACPCSLNPs. Moreover, the inner polymeric core could not only induce the generation of electrostatic interactions between the polymer and drug molecules but could also affect the prominent repulsions between the polar head groups of lipids and the nonpolar drug molecules. As a result, the sustained maximum release of the drug molecules (~48.5%) into the system was observed over a long period (~4 days). Furthermore, cell cytotoxicity studies were conducted in a human cervical cancer cell line (HeLa) and a healthy human dermal fibroblast cell line (HDFa) by employing all AC loaded LNPs along with free drugs. Multicolor cell imaging was also observed in HeLa cells using ACPCSLNPs. Notably, more curcumin was released from the ACPCSLNPs than AC due to the presence of polar group attractions and polar-polar interactions between the lipid head groups and curcumin since curcumin is more soluble than AC in aqueous medium. In addition, the predictions of the release kinetic patterns were also investigated thoroughly using the exponential-based Korsmeyer-Peppas (K-P) and Higuchi models for drug-loaded LNPs and PLGA NPs, respectively.

Antibiofilm Potential of Silver Sulfadiazine-Loaded Nanoparticle Formulations: A Study on the Effect of DNase-I on Microbial Biofilm and Wound Healing Activity.

Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 μg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing.

Nanoclusters prepared from ruthenium(II) and quercetin for fluorometric detection of cobalt(II), and a method for screening their anticancer drug activity.

Ruthenium-quercetin conjugated nanoclusters (Ru-QC NCs) were synthesized via a one-pot reflux reaction. As inhalation of heavy metal ions like cobalt can lead to lung cancer, a fluorescent probe was designed for the determination of Co(II) both in aqueous solutions and living cells. The probe consists of hybrid nanoclusters with an average size of 2nm that were prepared from ruthenium(II) ions and the flavonoid quercetin. These are termed as Ru-QC NCs. They display strong orange-colored emission with a peak at 558nm under 465-nm excitation. The Ru-QC NCs are cell viable and enable imaging of cells and intracellular fluorometric detection of Co(II). The anticancer properties of Ru-QC NCs were screened by using non-small cell lung cancer (A549) and human dermal fibroblast (HDFa) cell lines. The Ru-QC NCs exert considerable cytotoxicity in A549 cells (at levels of 20-50μg·mL-1), whereas no significant cytotoxicity was observed in case of HDFa cells. The anticancer properties of Ru-QC NCs were screened via MTT assay, live-dead staining, and ROS assay, respectively. Morphological changes of cancer cells were observed using atomic force microscopy. The fluorescent probe can detect Co(II) with a detection limit of 9.28nM and with a linear response in the 0.03-100μM concentration range. Graphical abstract Schematic representation of ruthenium-quercetin nanoclusters with potential anticancer properties. They are promising fluorescent probes for intracellular sensing of cobalt (Co2+) and bio-imaging. They exhibited efficient fluorometric detection of Co2+ with the limit of detection (LOD) of 9.28nM.

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.

Enhanced antibacterial activity of PEO-chitosan nanofibers with potential application in burn infection management

Chitosan (CS) is a well-known biological macromolecule having numerous applications due to its exceptional properties especially in the form of nanofibers. The antibacterial activity is compromised when co-polymers are added to electrospun CS but, the reproducibility can be enhanced which is key to commercialization. We have tried to enhance the antibacterial activity of chitosan based nanofibers with the addition of Zinc oxide (ZO) nanoparticles and ciprofloxacin (model drug) at very low concentrations. The rheology of solutions was studied along with the process parameters for the optimization of nanofibers using response surface methodology. Nanofibers having diameter of 116 nm with a SD of only 21 nm were optimized. ZO loaded nanofibers showed better thermal stability. Different drug release models were fitted to drug release profile. The release was pH dependent best followed by Zero order and Hixson Crowell release models. Good antibacterial activity and non-toxicity was observed against human dermal fibroblast and keratinocytes cell lines (>82.5%) which justifies its potential to eliminate or prevent infection in burn wounds with less side effects due to low amount of drug.

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).