Fibroblast Cell Line L929 Research Articles

In Situ Forming Silk Sericin-Based Hydrogel: A Novel Wound Healing Biomaterial.

In situ cross-linked hydrogels have the advantage of effectively fulfilling the wound in its shape and depth. Amongst the new generation of natural-based biopolymers being proposed for wound care and skin regeneration, silk sericin is particularly interesting due to its exceptional properties such as biocompatibility, biodegradability, and antioxidant behavior, among others. In this study, a new enzyme-mediated cross-linked hydrogel composed of silk sericin is proposed for the first time. The developed hydrogel cross-linking strategy was performed via horseradish peroxidase, under physiological conditions, and presented gelling kinetics under 3 min, as demonstrated by its rheological behavior. The hydrogels presented a high degree of transparency, mainly due to their amorphous conformation. Degradation studies revealed that the hydrogels were stable in phosphate buffer solution (PBS) (pH 7.4) for 17 days, while in the presence of protease XIV (3.5 U/mg) and under acute and chronic physiological pH values, the stability decreased to 7 and 4 days, respectively. During protease degradation, the present sericin hydrogels demonstrated antioxidant activity. In vitro studies using an L929 fibroblast cell line demonstrated that these hydrogels were noncytotoxic, promoting cell adhesion and massive cell colonization after 7 days of culture, demonstrating that cells maintained their viability and proliferation. In addition, the application of sericin-based hydrogel in an in vivo diabetic wound model validated the feasibility of the in situ methodology and demonstrated a local anti-inflammatory effect, promoting the healing process. This study presents a simple, fast, and practical in situ approach to produce a sericin-based hydrogel able to be applied in low exudative chronic wounds. Moreover, the study herein reported fosters the valorization of a textile industrial by-product by its integration in the biomedical field.

Antibacterial effect against both Gram-positive and Gram-negative bacteria via lysozyme imprinted cryogel membranes

The development of novel biocompatible and cost effective cryogel membrane which shows enhanced antimicrobial properties in order to use for several approaches such as wound dressing, scaffold or food packaging was aimed in this study. A super macro porous lysozyme imprinted cryogel membranes showing antibacterial effect against both Gram-positive and Gram-negative bacteria were prepared by using molecular imprinting technique. N-methacryloyl-(L)-histidine methyl ester (MAH) was used as the pseudo specific ligand and complexed with Cu++ in order to provide metal ion coordination between MAH and template molecule (lysozyme). Comparing the antibacterial activity of different lysozyme concentrations, cryogel membranes were prepared in three different concentrations. To synthesize Poly (hydroxyethyl methacrylate-N-methacryloyl-(L)-histidine methylester) P(HEMA-MAH) cryogel membrane, free radical polymerization initiated by N, N, N′, N′-tetramethylene diamine (TEMED) and ammonium persulfate (APS) was carried out at −12 °C. The characterization of the lysozyme imprinted cryogel membrane was accomplished by using scanning electron microscopy (SEM), swelling degree measurements and Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) spectroscopy. The cytotoxicity test of produced membrane was performed by using mouse fibroblast cell line L929. The antibacterial activity of P(HEMA-MAH) lysozyme molecular imprinted [P(HEMA-MAH) Lyz-MIP] cryogel membranes against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were determined by Kirby-Bauer membranes diffusion and viable cell counting methods. When the antibacterial effect of P(HEMA-MAH) Lyz-MIP cryogel membranes were evaluated, it was found that P(HEMA-MAH) Lyz-MIP cryogel membranes had stronger antibacterial effects against Gram-negative E. coli bacteria even in low lysozyme concentrations. In addition, 100% bacterial inhibition was detected for both of two bacteria at increasing lysozyme concentrations.

Mikrodalga Hızlandırmalı Yöntemi İle Limon Kabuk Ekstraktsiyonu Kullanarak Non-toksik Gümüş Nanopartiküllerin Sentezlenmesi

In this study, biofunctionalized globular or oval shaped silver nanoparticles were obtained by using aqueous extract of lemon peel (Citrus limon) via microwave-accelerated heating system. While UV−visible spectroscopy, FTIR and XRD analyses were applied to recognize the formation of nano-silver, TEM and Zeta analysis were employed to reveal their morphological features. UV–vis spectrum of fabricated AgNPs indicated its characteristic maximum absorbance at 445 nm. Phytosynthesized silver nanoparticles were poly-dispersed with Z-average value of 41.86 nm, and showed excellent stability for several months with no aggregation and agglomeration. The non-toxic nature of the developed Ag nanoparticles was further confirmed by applying on healthy mouse fibroblast L929 cell line, which may expand their potentials for further studies related to medical science and other biological applications.

Preclinical assessment of stem of Nicotiana tabacum on excision wound model

Agro-waste material derived from N. tabacum has shown enormous potential antioxidant and antimicrobial activity. Hence in the present study, we investigated the wound healing efficacy of ethanolic extract of stem of Nicotiana tabacum on wistar rat model. Ethanolic extract prepared from defatted stem was to check various phytochemicals using spectrophotometric and chromatographic technique. The antioxidant potential was determined by FRAP and Reducing Power assay in extract. Cytotoxicity of extracts was determined using mouse fibroblast L929 cell lines by MTT assay. In vivo angiogenic activity was observed on chick chorioallantoic membrane (CAM) model by observing blood vessels formation and its branching. In vivo wound healing activity was observed on excision wounds in rat model by quantifying percentage of wound contraction, antioxidant activity and histopathology studies. From the present study, polyphenols, tannins and alkaloids were found to be determined in the ethanolic extract by means of spectrophotometric and chromatographic analysis against standards. Antioxidant assay revealed maximum antioxidant potential in ethanolic extract. Cytotoxic effect of extract has not been shown on L929 cell line. From CAM model, extract has shown growth of blood vessels formation at concentration of 480 µg/ml. Topical application of extracts on excision wounds, revealed wound healing activity i.e. 98.7% ± 0.002 on 14th day as well as enzymatic activity (SOD, CAT, GST) and non enzyme content (GSH and Lipid peroxidation) has been found to be high in granulated tissue. Hisopathological studies confirmed the re-epithelization in skin wounds. It can be concluded that stem of N. tabacum can be used as herbal remedy in wound healing process as a topical application.

Development of robust, ultra-smooth, flexible and transparent regenerated silk composite films for bio-integrated electronic device applications

Regenerated Silk Fibroin (RSF) films are considered promising substrate candidates primarily in the field of bio-integrated electronic device applications. The key issues that ought to be addressed to exploit the inherent advantages of silk thin films include enhancing their flexibility and chemical durability. Such films find a plethora of applications, the significant one being conformal, transparent microelectrode arrays. Elevated temperatures that are regularly used in lithographic processes tend to dehydrate RSF films, making them brittle. Furthermore, the solvents/etchants used in typical device fabrication results in the formation of micro-cracks. This paper addressed both these issues by developing composite films and studying the effect of biodegradable additives in enhancing flexibility and chemical durability without compromising on optical transparency and surface smoothness. Through our rigorous experimentation, regenerated silk blended with Polyvinyl Alcohol (Silk/PVA) is identified as the composite for achieving the objectives. Furthermore, the Cyto-compatibility studies suggest that Silk/PVA, along with all other silk composites, have shown above 80% cell viability, as verified using L929 fibroblast cell lines. Going a step further, we demonstrated the successful patterning of 32 channel optically transparent microelectrode array (MEA) pattern, with a minimum feature size of 5 μm above the free-standing and optically transparent Silk/PVA composite film.

Starch modified alginate nanoparticles for drug delivery application

Natural polymers have been widely studied as vehicles that have gained much interest in the encapsulation and delivery of drugs and bioactive molecules. In this study, we developed starch-modified alginate nanoparticles using a green facile technique for drug delivery application. The potential of the prepared nanoparticles for controlled drug delivery applications is demonstrated using theophylline and bovine serum albumin as model drugs. The nanoparticles possessed the encapsulation efficiency of 60 to 75%. The results of in vitro drug release studies showed the pH dependent characteristics of the prepared nanoparticles. In vitro cytotoxicity test revealed the biocompatibility of the developed nanoparticles against L929 fibroblast cell lines. The in vitro cellular uptake of nanoparticles was visualized in L929 fibroblast cells using fluorescent microscopy. The preliminary investigation suggests the developed nanoparticle is a promising candidate for drug delivery application.

Hydrothermal-Assisted Synthesis and Stability of Multifunctional MXene Nanobipyramids: Structural, Chemical, and Optical Evolution.

Recent advancements in two-dimensional materials have brought MXene (Ti3C2) into attention due to its exciting properties as a very promising material for various applications. In this work, we report a novel Ti3C2 nanobipyramid (Ti3C2 NB) structure obtained through a three-step process involving exfoliation, delamination, and subsequent hydrothermal treatment. The morphological and textural properties at each step of synthesis were studied using an array of experimental techniques such as transmission electron microscopy, scanning electron microscopy, and atomic force microscopy and the chemical properties through X-ray diffraction, Raman, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis. The Ti3C2 NBs exhibit fluorescence with an excitation-dependent emission. Further, the effect of temperature and pH on the fluorescence was also investigated, which opens up its scope in bioanalytical applications. Ti3C2 NBs showed a ∼43% increase in photoluminescence intensity from pH 3 to 11 while a ∼38% increase with the temperature from 20 to 80 °C. Usually, MXenes are highly susceptible to oxidation, but the Ti3C2 NBs were found to be chemically and optically stable even after 30 days. Bestowed with good hydrophilicity, the material exhibited high biocompatibility on the mouse fibroblast cell line L929. Further, L929 cells also showed good cellular adhesion on a Ti3C2 NB-modified glass substrate. These properties pave a way for its multifunctional ability as a sensor for pH and temperature as well as bioimaging.

Facile design of lidocaine-loaded polymeric hydrogel to persuade effects of local anesthesia drug delivery system: complete in vitro and in vivo toxicity analyses

The principal goal of the present investigation was to enterprise new and effective drug delivery vesicle for the sustained delivery of local anesthetic lidocaine hydrochloride (LDC), using a novel combination of copolymeric hydrogel with tetrahydroxyborate (COP–THB) to improve bioactivity and therapeutic potential. To support this contention, the physical and mechanical properties, rheological characteristics, and component release of candidate formulations were investigated. An optimized formulation of COP–THB containing LDC to an upper maximum concentration of 1.5% w/w was assessed for drug crystallization. The biocompatibility of the prepared COP–THB hydrogel was exhibited strong cell survival (96%) and growth compatibility on L929 fibroblast cell lines, which was confirmed by using methods of MTT assay and microscopic observations. The COP–THB hydrogel release pattern is distinct from that of COP–THB/LDC hydrogels by the slow-release rate and the low percentage of cumulative release. In vivo evaluations were demonstrated the anesthetic effects and toxicity value of treated samples by using mice models. In addition, COP–THB/LDC hydrogels significantly inhibit in vivo tumor growth in mice model and effectively reduced it is in vivo toxicity. The pharmacological evaluation showed that encapsulation of LDC in COP–THB hydrogels prolonged its anesthetic action with favorable in vitro and in vivo compatibility. This novel design may theoretically be used in promising studies involving the controlled release of local anesthetics. Highlights Development a modified sustained release system for the local anesthetic lidocaine. PVP-THB hydrogel to improve the pharmacological properties of the drug and their anesthetic activities. Profiles of PVP-THB/LDC showed that the effective release of associated lidocaine. This new formulation could potentially be used in future local anesthetics.

Presencia de Chlamydia abortus en cabras con historial de abortos en México

Chlamydia abortus causes a series of reproductive disorders in ruminants, including abortions, premature births and stillbirths. Additionally, as a zoonosis, it can cause miscarriages or pneumonia in people who come in contact with sick animals or their secretions. The objective of this study was to isolate C. abortus from Mexican goats with a history of abortion and from recently parturient goats with a history of abortion; 186 samples were collected from 49 herds in the states of Coahuila, Jalisco, Puebla, Veracruz and Querétaro. Bacterial isolation of the clinical samples was performed using the mouse fibroblast cell line L929 and molecular identification was achieved by amplification of a 342 bp fragment corresponding to the 16S-23S ribosomal intergenic spacer RNA region. The amplification products were sequenced and compared with the GenBank database. Isolation identified 23.1% of the samples and PCR identified 9.6% as positive. Homology search revealed 100% identity with Chlamydia abortus EF486854, U76710, U68444, among others. The presence of C. abortus was confirmed in goats with a history of abortion in Mexico by bacterial isolation, PCR and sequencing. These findings suggest that C. abortus played a substantial role in goats with a history of abortion in Mexico.

A novel greener synthesis of ZnO nanoparticles from Nilgiriantusciliantus leaf extract and evaluation of its biomedical applications

The present investigation aims at the synthesis of zinc oxide nanoparticles (ZnO NPs) from Nilgiriantusciliantus leaf extract. ZnO NP was synthesized by using zinc sulphate as a precursor with simple microwave assisted green method. The obtained zinc oxide nanoparticles were characterized by XRD, FT-IR, UV –Vis, SEM and TEM analysis. ZnO NPs obtained was screened in vitro for its antibacterial activity against both gram positive (S .aures and S .mutans) and gram negative (E .coli and P.aeruginosa) bacteria by agar well diffusion method. In addition to this, inhibitory effect of ZnO NP against MCF-7 breast cancer cells and normal L929 fibroblast cell lines was examined by MTT assay. The experimental results show that ZnO NP synthesized in the present study possesses excellent antibacterial, and anticancer activity. Further it is also nontoxic towards normal L929 fibroblast cell lines. Thus the present study on green synthesized ZnO NP will be helpful for facilitating its future research progress focusing on biomedical fields.

Cytotoxicity evaluation of different commercially available absorbent feminine hygiene products and a transdermal patch using direct contact and extract exposure methods

We investigated the cytotoxic potential of three different commercially available absorbent feminine hygiene products and one transdermal patch using direct contact and extract exposure methods. Two different cell lines were used – mouse fibroblast L929 and normal human skin fibroblast CCD-986sk cell lines. The test samples were extracted using three different methods in accordance to International Organization for Standardization (ISO). Viability of cells was analyzed using MTT assay and morphology of the cells were also observed using phase contrast microscopy. Overall, the direct contact method using L929 cells showed that all the test samples had no toxic effect when exposed to extracts for 1 h. For the exposure method, no toxic effect was observed in both L929 and CCD986sk cells incubated with all the test samples regardless of the extraction methods used.

Biofilm Expressing Genes in Bacteria Causing Urinary Catheter Associated Infections

Biofilm associated infection causes higher mortality in catheterized patients. Identification of cupA gene in Pseudomonas aeruginosa coding for biofilm formation was selected as a primary objective. Synergistic antibacterial drugs (moxifloxacin-metronidazole) were prepared using the selected concentrations for coatings onto urinary catheter samples. Antibacterial coatings of synergistic antibacterial drugs onto a urinary catheter and its antibacterial activity were evaluated using the standard diffusion method. The drug coated catheters were investigated for their biocompatible properties. The biocompatibility of the drug coated samples was investigated on L929 fibroblast cell lines using MTT assay. The biofilm expressing genes (cupA gene) of the selected organism was detected using molecular methods. During the analysis, the cupA gene from the target organism was confirmed by the PCR method aided with the DNA electrophoresis process. The study was confirmed from the obtained DNA fragments of 172bp by comparing with 170bp fragment of reference bacterial strain. Quantitative antibacterial activity results showed that the drug coated catheter samples were significantly reduced the bacterial numbers. Biocompatibility of coated catheter samples evaluated by in-vitro cell culture cytotoxicity assay exhibited no effect on cell viability of fibroblast cell lines. It is concluded that identifying biofilm expressing genes could help the health care workers to diagnose and treat the patients with an appropriate antibacterial agent.

Profiles of nutritional, bioactive compounds and cytotoxic activity of Dwarf date palm (Phoenix loureiroi) fruit

The wild edible fruits are basic food sources and these contain potential dietary compounds which provide a healthy diet. Such wild edible fruits play an important role in supplementing the diet and livelihood of rural/tribal communities. Thus, the present study determined the nutritive values of Phoenix loureiroi fruit by screening the phytochemical compounds, organic acids and polyphenolics along with the evaluation of cytotoxic activity. The nutritional composition revealed high contents of total proteins (36.30 mg BSAE/g dry fruit), total free amino acids (6.15 mg LE/g dry fruit), reducing sugars (85.40 mg GE/g dry fruit), vitamin E (2.50 mg TE/g dry fruit) and sodium (1.26 mg/g dry fruit) at Rutab stage of maturation. Anti-nutritional compositions of fruit were found to be chymotrypsin inhibitors (3.31 CIU/mg protein), trypsin inhibitors (0.01 TIU/mg protein) and phytate (0.42 g phytate/100 g dry fruit) contents. High-performance thin-layer chromatography (HPTLC) separation demonstrated that fruit contains a high amount of essential (tryptophan, 41.30 mg/g dry fruit) and non-essential (tyrosine, 25.70 mg/g dry fruit) amino acids. The total phenolics concentration was found to be 49.68 mg GAE/100 g dry fruit. Liquid chromatography analyses revealed that the fruit contained high amounts of fructose (0.12 mg/g dry fruit), ascorbic acid (2.80 mg/g dry fruit), catechin (3.78 mg/g dry fruit) and succinic acid (1.57 mg/g dry fruit). The bioactive compounds of fruit extract inhibited the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 8.51 µg/mL). The cell viability value (65.87%) on fibroblast L929 cell lines indicates fruit extract was safe up to 1000 µg/mL concentration. The results revealed that the P. loureiroi fruit was rich in nutraceutical compounds and could be used for the development of safe natural products.

Antibacterial and anticancer activity of biosynthesised CuO nanoparticles.

The present investigation aims for the synthesis of copper oxide nanoparticles (CuO NPs) using Nilgirianthus ciliatus plant extract. The obtained CuO NPs were characterised by X-ray diffraction, Fourier transform infrared spectrum, ultraviolet-visible spectroscopy, photoluminescence, scanning electron microscopy and transmission electron microscopy analysis. Significant bacterial activity was manifested by CuO nanoparticles against both Gram-positive (Staphylococcus aureus and Staphylococcus mutans) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The synthesised CuO NPs have good cytotoxicity against both human breast cancer cell line (MCF-7) and lung cancer cell line (A549) with minimum cytotoxic effect on normal L929 (fibroblast) cell lines.

Synthesis and Characterization of Phenylalanine Nanotubes as Green pH‐Responsive Drug Nanocarriers

AbstractThe present study is aiming to investigate the potential of phenylalanine amino acid nanotubes (PhNTs) synthesized by a self‐assembly process as an efficient and pH‐responsive green drug nanocarrier for the treatment of oral disease. Phenylalanine was used for the preparation of solutions with three different concentrations (0.1, 0.5 and 2.5 mg/ml). Scanning electron microscopy (SEM) and Field emission scanning electron microscopy (FESEM) images showed that low and high concentrations of phenylalanine solution creates nanospheres and nanowires, respectively rather than tubular‐shaped nanostructures. In contrast, phenylalanine nanotubes were synthesized by medium concentration (0.5 mg/ml). The tubular shape and nanoscale diameter of the synthesized PhNTs were characterized by FESEM, Transmission Electron microscopy (TEM), Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR). These characterization tests confirmed the synthesis of PhNTs with a tubular shape and nanoscale diameter. In the second stage, metronidazole was loaded into the phenylalanine‐based nanostructures as an effective drug for oral disorders. The results indicated that nanospheres and nanowires show drug loading efficiency of 49 % and 58 %, respectively, after 48 h of incubation time. Whereas, the drug loading efficiency for nanotubes was 91 %. The results from the FTIR analysis and UV‐vis spectroscopy verified the presence of metronidazole into the hollow structure of PhNT. While a burst drug release was observed for nanospheres and nanowires, PhNTs showed a well‐controlled release of metronidazole up to 95 % at oral pH, which is best fitted to the Weibull model. Subsequently, the cell viability of phenylalanine‐based nanostructures was assessed by MTT test on L929 fibroblast cell line.

Antibiotic‐based silk fibroin films for burn wound healing

Silk fibroin (SF), which is a protein‐based biomacromolecule, proved to be an important biomaterial in biomedical applications and tissue engineering. The present study mainly focused to investigate the effective antibiotic against the common pathogens found at the site of burn wounds. The SF films prepared with selected antibiotics had shown activity against the target bacterial pathogens, but no activity was found against fungal species. The release of antibiotics from films resulted in the microbial susceptibility. Results have shown Ciprofloxacin—6 μg, Amoxicillin—15 μg, and Nystatin—70 μg at minimal inhibition concentration (MIC) has shown maximum zone of inhibition when compared with other antibiotics. The antibiotic‐based silk fibroin (ABSF) films have shown a positive effect on cell viability and cell adhesion on the L929 fibroblast cell line. The structural conformations of films were also carried out by FTIR and XRD, an increase in the crystalline size was observed in the antibiotic‐based film. Results demonstrate that ABSF films can act against the pathogens without losing their drug nature, can reduce the chance of infections at the site of the wound, and also can establish the basis for the accelerated healing process of the burn wound.

Superabsorbent crosslinked bacterial cellulose biomaterials for chronic wound dressings

In this work, we present a novel ex situ modification of bacterial cellulose (BC) polymer, that significantly improves its ability to absorb water after drying. The method involves a single inexpensive and easy-to-perform process of BC crosslinking, using citric acid along with catalysts, such as disodium phosphate, sodium bicarbonate, ammonium bicarbonate or their mixtures. In particular, the mixture of disodium phosphate and sodium bicarbonate was the most promising, yielding significantly greater water capacity (over 5 times higher as compared to the unmodified BC) and slower water release (over 6 times as compared to the unmodified BC). Further, our optimized crosslinked BC had over 1.5x higher water capacity than modern commercial dressings dedicated to highly exuding wounds, while exhibiting no cytotoxic effects against fibroblast cell line L929 in vitro. Therefore, our novel BC biomaterial may find application in super-absorbent dressings, designed for chronic wounds with imbalanced moisture level.

Genistein nanoformulation promotes selective apoptosis in oral squamous cell carcinoma through repression of 3PK-EZH2 signalling pathway

BackgroundOverexpression of polycomb protein contributes to epigenetic repression in oral squamous cell carcinoma (OSCC) ensuing in poor prognosis and aggressive phenotype. Several plant-based compounds could help prevent epigenome alteration and cancer progression, but their low bioavailability limits their therapeutic activity. HypothesisIn this study, we have synthesized genistein nanoformulation (GLNPs) and evaluated its epigenetic regulation mechanism for selective apoptosis induction in OSCC. MethodsLactalbumin was used to prepare nanoformulation of Genistein. The mechanism of epigenetic regulation and selective apoptosis by Genistein loaded nanoparticles was studied in OSCC cell line JHU011 and fibroblast cell line L929 using immunofluorescence, Western blotting and ChIP-qPCR assay. ResultsWe have found that GLNPs treatment selectively induced apoptosis in OSCC compared to the normal fibroblast cells. This selective effect in OSCC is achieved through enhanced reactive oxygen species (ROS) generation followed by Bax mitochondrial translocation and caspase 3 activation. Further, GLNPs induced withdrawal of epigenetic transcription repression through concurrent downregulation of the polycomb group proteins (PcG) Bmi 1 and EZH2 along with their successive targets, UbH2AK119 and H3K27me3, which have immense therapeutic implications in the treatment of OSCC. Last, we have established that GLNPs regulate EZH2expression through proteasomal mediated degradation and 3PK inhibition; 3PK protein was found physically linked with EZH2 protein and its promoter region (-1107 to -1002). This event indicates that 3PK might play some crucial role in EZH2 expression and epigenetic control of OSCC. Moreover, the formulation showed improved biodistribution, aqueous dispersibility and enhanced biocompatibility In-vivo. ConclusionsThese results provide evidence that GLNPs may withdraw epigenetic transcriptional repression and selectively induce apoptosis in human oral squamous cell carcinoma.

Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.

Novel Benzimidazole Derivatives: Cytotoxic and Apoptotic Properties on Lung Cancer Cell Line

Background: Benzimidazole derivatives are privileged molecules known to have a wide variety of biological activities. In medicinal chemistry, due to the ring’s structural similarity to nucleotides, its derivatives were investigated as new chemotherapeutic agents. Our research group have been studying 1,2-disubstituted benzimidazoles, including thiocarbamoyl group and their potential anticancer activity. Based on previous findings, we synthesized novel 1-[2-(4-substituted phenyl-2-oxoethyl)]-2-[(2/3/4-substituted phenylpiperidin-1-yl)thiocarbamoyl]benzimidazole derivatives (3a-o). Methods: The obtained fifteen derivatives were studied on A549 adenocarcinomic human alveolar basal epithelial cell line and mouse L929 fibroblastic cell line to determine their cytotoxic activity. These compounds were also investigated to identify their apoptotic properties. Results and Discussion: The structures of the compounds based on three different groups differ from each other with the phenyl substituents bonded to the piperazine ring. All of the compounds showed remarkable antitumor activity, but the first five compounds bearing non-substituted phenyl moiety exhibited selective cytotoxicity when compared in terms of potencies to the normal cell line. Conclusion: Compounds 3j, 3m and 3n were identified as the most apoptotic derivatives; however, compounds 3e and 3h provoked apoptosis with the percentages of 10.6 and 10.9% and selective cytotoxicity.