Cytotoxicity Evaluation Research Articles

Front Cover: Synthesis of Para‐Acetylated Functionalized Ni(II)‐POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines (Chem. Biodiversity 9/2024)

Front Cover: Synthesis of <i>Para</i>‐Acetylated Functionalized Ni(II)‐POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines (Chem. Biodiversity 9/2024)

Optimization of Microwave-Assisted Green Synthesis of Zinc oxide nanoparticles Using Ocimum americanum and Euphorbia hirta Extracts: In Vitro Evaluation of Antioxidant, Anti-inflammatory, Antibacterial, Cytotoxicity, and Wound Healing Properties

Optimization of Microwave-Assisted Green Synthesis of Zinc oxide nanoparticles Using Ocimum americanum and Euphorbia hirta Extracts: In Vitro Evaluation of Antioxidant, Anti-inflammatory, Antibacterial, Cytotoxicity, and Wound Healing Properties

Evaluation of surface roughness, cytotoxicity, and antibacterial effects of silver nanoparticle coating on copper nickel titanium orthodontic arch wires - in vitro study.

Surface roughness of arch wires directly impacts their corrosion behavior, friction resistance, and plaque accumulation, which may hinder tooth movement and lead to dental caries. The study aims to synthesize vanillin-mediated silver nanoparticles (AgNPs), characterize them, assess surface roughness and cytotoxicity of arch wires after silver nanoparticle coating, and test their antibacterial properties. Nine copper-nickel-titanium arch wires (CuNiTi) were cut into equal pieces. Three were sent for surface roughness assessment, three for cytotoxicity, and three for antibacterial testing. Dip coating of wires was done using the sol-gel thin film method. The surface roughness (Ra) before and after coating was evaluated using scanning electron microscopy and atomic force microscopy. Cytotoxicity testing was done with a (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay using gingival fibroblasts. Statistical analysis was done using SPSS software. Antibacterial activity against S. mutans was tested using the Agar-well diffusion method. The CuNiTi wires were coated successfully, and the coating appeared homogeneous. The mean Ra after coating (297.3+/- 30.4 nm) was significantly less than that before coating (339.7+/-49.2 nm). AgNPs showed minimal cytotoxicity against human gingival fibroblasts at different concentrations. Optical microscopy showed over 90% viability between 12.5 and 100 µg/ml. At 100 µg/ml, only 80% of cells remained viable. AgNP coating is biocompatible at concentrations up to 75 µg/ml. There was a significant intergroup difference in the zone of inhibition (antibacterial activity) noted with higher values in noncoated wires. (P value <0.007). AgNPs coated on CuNiTi arch wires showed reduced surface roughness and minimal cytotoxic effects on human gingival cells and good antibacterial activity against S. mutans compared to noncoated arch wires.

Andrographis echioides mediated synthesis of ZnONPs: A mechanistic insight into their antibacterial and anticancer efficacy

Finding alternatives to traditional antibiotics has become crucial due to the emerging antibiotic resistance shown by various microorganisms. Metal nanoparticles are arising as one such alternative. This paper presents an efficient and environmentally benign approach for preparing ZnO nanoparticles via greener approaches using Andrographis echioides (L.) Nees leaf extract and unravel the possible applications and mechanisms behind their toxicity against Escherichia coli and Staphylococcus aureus. The characterization studies show a peak at 362 nm (λmax) in the UV–Vis spectroscopic measurement with a bandgap energy of 3.10 eV. Hexagonal wurtzite structure is revealed in the XRD investigation of Ae-ZnONPs with a crystallite size of ≈14 nm. Ae-ZnONPs’ spherical structure andtheir meansize ranging between 15 and 35 nm, areconfirmed by SEM and TEM assessment respectively. The FTIR analysis revealed various functional groups and molecular interactions of plant extract and Ae-ZnONPs. Investigation into the antibacterial mechanism of action of Ae-ZnONPs revealed that these nanoparticles exhibit bactericidal effect against Escherichia coli and Staphylococcus aureus through the means of generation of reactive oxygen species (ROS), causing elevated lipid peroxidation and breakage of the membrane, and subsequent events culminating in cell death. These nanoparticles showed distinct antioxidant properties by scavenging DPPH, SOD, ABTS, and FRAP free radicals. Ae-ZnONPs were biocompatible with human RBC indicating their biosafe nature. Cytotoxicity evaluation of Ae-ZnONPs alone revealed concentration-dependent toxicity towards HeLa cells while remaining non-toxic to normal cells at the maximal concentration (100 μg/mL), showcasing anticancer potential which was further elucidated via ROS, live/dead cell imaging, and apoptotic study. Molecular alterations in HeLa cells were investigated through RT-PCR that showed upregulation of apoptotic and downregulation of antiapoptotic genes. The comprehensive findings suggest that Ae-ZnONPs can be employed as alternatives to antibiotics which also exhibit potential as anticancer agents, laying the foundation for future extensive research in this domain.

Centaurea iberica trevir. Ex spreng. Phytochemical content and evaluation of cytotoxicity, phytotoxicity, anti-inflammatory, larvicidal and anti-inflammatory potentials

Due to their tremendous therapeutic ability to treat a wide range of illnesses, medicinal plants are employed as a rich source and nutraceuticals practically in all civilizations. The goal of the current study was to evaluate phytochemistry and biological potentials of medicinal plant Centaurea iberica as previously no research work has been reported. To prepare plant extracts, five different solvents, methanol, ethanol, n-hexane, ethyl acetate and chloroform were used. Total phenolic content of the investigated plant was recorded highest in the methanolic extract ranges from 91 ± 1.2 mg/g, total flavonoid content recorded 24 ± 1.1 mg/g. Moreover, maximum LC50 value (9.95 µg/mL) was recorded for methanolic extract using cytotoxicity assay. Radish seed germination phytotoxicity assay indicated the highest phytotoxic potential in n-hexane (55 % seed inhibition) extract of C. iberica. However, in anti-inflammatory assay less than 50 % inhibition was observed for methanolic extract and plant was found to be inactive against larvicidal activity. Based on the results of this study, it is recommended that more in vitro and in vivo research activities be done in the future, as well as chemical characterization to identify various compounds that may be utilized to treat various illnesses.

Cytotoxicity and cell migration evaluation of a strontium silicate-based root canal sealer on stem cells from rat apical papilla: an in vitro study

BackgroundCalcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field.ObjectiveTo comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs).MethodsrSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays .ResultsNo significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration.ConclusionsCRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment.

Harnessing the hidden environmental power of Bjerkandera adusta laccase: Sustainable production, green immobilization, and eco-friendly decolorization of mixed azo dyes

This research unveils the untapped potential of laccase, derived from the Bjerkandera genus, utilizing it in an immobilized system aimed at detoxifying harmful azo dye effluents from the textile industry, thus contributing to environmental protection. Marking a pioneering achievement, we recorded the highest laccase activity at 94.52 U/g cultivating B. adusta's mycelium on brewer's spent grain, enhanced with lignocellulosic waste, under meticulously optimized conditions −2.69 g of alkali-pretreated beech sawdust, 0.91 g of cypress cone, and 8-day incubation period. The harvested laccase was subjected to an immobilization process on alkali-pretreated beech sawdust, where, through optimization, we established the ideal conditions (30 mg of carrier, pH 7, and 3.5 h), achieving an immobilization efficiency of 72.24% with a residual activity of 57.64%. Remarkably, both free and immobilized forms of the B. adusta TMF1 laccase enzyme demonstrated formidable efficacy in decolorizing a mix of three distinct azo dyes (Orange G, Eriochrome Black T, and Congo Red), eliminating over 63% of the coloration within just 30 min. The immobilized laccase showed consistent performance across four decolorization cycles. Moreover, the breakdown products of the azo dye mix were analyzed using the HPLC method, complemented by evaluations of potential antimicrobial activity, phytotoxicity and cytotoxicity, revealing a non-toxic composition without cytotoxicity, highlighting the process's safety for environmental release. The significance of this research is reflected in the distinguished construction of a green biocatalyst acting as a stable and time-efficient in remediation of targeted azo dye pollution from the textile industry following the principles of circular economy.

Synthesis of Para-Acetylated Functionalized Ni(II)-POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines.

A series of three Ni(II)-POCOP complexes para-functionalized with an acetoxyl fragment were synthesized. All complexes (2 a-c) were fully characterized through standard analytical techniques. The molecular structure of complex 2 b was unambiguously determined by single-crystal X-ray diffraction, revealing that the metal center is situated in a slightly distorted square-planar environment. Additionally, the acetoxy fragment at the para-position of the phenyl ring was found to be present. The in vitro cytotoxic activity of all complexes was assessed on six human cancer cell lines. Notably, complex 2 b exhibited selective activity against K-562 (chronic myelogenous leukemia) and MCF-7 (mammary adenocarcinoma) with IC50 values of 7.32±0.60 μM and 14.36±0.02 μM, respectively. Furthermore, this compound showed negligible activity on the healthy cell line COS-7, highlighting the potential therapeutic application of 2 b. The cytotoxic evaluations were further complemented with molecular docking calculations to explore the potential biological targets of complex 2 b, revealing interactions with cluster differentiation protein 1a (CD1 A, PDB: 1xz0) for K-562 and with the progesterone receptor for MCF-7.

Synthesis and Evaluation of Cytotoxicity of Carbon Dots Functionalized with Diosgenin

Synthesis and Evaluation of Cytotoxicity of Carbon Dots Functionalized with Diosgenin

Evaluating the biomedical and environmental safety of selenium nanoparticles synthesized from black pepper seed extract

In recent times, sustainable synthesis of selenium nanoparticles (Se NPs) has seen a significant rise in research, focusing primarily on microbial and plant polysaccharide-based approaches for various bioapplications. However, there are limited studies on the use of extracts from herbal spice plants as capping agents for Se NPs. Therefore, this study investigates the pioneering synthesis of Se NPs using black pepper (Piper nigrum) seed extract (PSe NPs) and assesses their antioxidant properties, hemolytic potential, antibacterial and antibiofilm activities, cytotoxicity, phytotoxicity, in vivo toxicity in zebrafish embryos, and their effectiveness in prolonging the shelf life of food materials. The green-synthesized PSe NPs were thoroughly physicochemically characterized and found to be sphere-shaped with a medium diameter of 10–100 nm. The PSe NPs exhibited substantial antibacterial effects, being more effective against S. aureus (Gram-positive)than against S. typhi (Gram-negative). Furthermore, PSe NPs significantly inhibited MRSA biofilm growth at 500 μg/mL and showed notable antioxidant activity compared to standard gallic acid. Also at 500 μg/mL, PSe NPs induced significant hemolysis, whereas inferior concentrations did not. Cytotoxicity evaluations using the MTT assay revealed that PSe NPs significantly reduced the viability of human normal embryonic kidney (HEK 293) cells and human cervical cancer (HeLa) cells after 24 hours of treatment at concentrations of 0.1–500 μg/mL. This cytotoxic effect was associated with apoptosis, as shown by acridine orange/ethidium bromide staining. In phytotoxicity assays, PSe NPs revealed significant effects on seed germination and root and shoot growth of the mung bean (Vigna radiata). The zebrafish embryotoxicity assay indicated that PSe NPs at 500 µg/mL affected embryo morphology, mortality and survival rates 96 hours after fertilization. Furthermore, the application of PSe NPs gel coatings effectively reduced weight loss and extended the shelf life of fruits such as apples and pears, maintaining their natural appearance.

Cytotoxicity and Apoptotic DNA Fragmentation Evaluation of Ethanolic Extract of Phyllanthus niruri L. in Vero and Primary Feline Testicular Cells

Phyllanthus niruri or Dukung Anak is native to Southeast Asia, particularly in Malaysia and has been used as traditional preparations and as health supplements. However, previous studies have found that P. niruri can impair the male reproductive functions. With booming population of stray animals within the community, a new controlling method that is more affordable and safer must be developed. This study was aimed to explore the safety of P. niruri as a male herbal contraceptive to be used in veterinary medicine as one of the non-surgical sterilisation methods. For the preliminary part of this ongoing research, we have investigated the cytotoxicity activity of P. niruri ethanolic extract on Vero and primary feline testicular cells (FTC) and DNA apoptotic activity in FTC. Phyllanthus niruri extract was prepared using cold maceration method in 50% ethanol. The FTC were prepared from feline testes obtained from post-routine castration from local private veterinary clinics, while Vero cells were obtained from the archived cells of Virology Laboratory, Faculty of Veterinary Medicine Universiti Malaysia Kelantan (FPV UMK). The MTT assay was performed to evaluate the cytotoxicity of these plant extracts on FTC and Vero cells. Apoptosis was assessed using DNA laddering assay on extracted DNA of the treated FTC cells and observed the DNA patterns in gel electrophoresis. The 50% cytotoxic concentration (CC50) of the ethanolic extract of P. niruri was a dose dependent. The DNA laddering assay revealed that the plant extract does not induce apoptosis in FTC. Therefore, the study outcomes indicated that the ethanolic extract of P. niruri is potentially safe for animal use. However, in vivo studies are required to confirm these findings.

Myrtle Essential Oil-Loaded Alginate Nanoparticles: A Dual Therapeutic Approach for Cytotoxicity Against Skin Cancer Cells and Antibacterial Effects on Common Pathogens

Background &amp; Objectives: The skin, being the body’s largest organ, is not only susceptible to one of the most prevalent forms of cancer but also vulnerable to a myriad of pathogens, including bacteria. Myrtle essential oil (EO) has been shown to possess both anticancer and antimicrobial properties. This study aimed to investigate the efficacy of alginate nanoparticles containing myrtle EO on melanoma (A375) and epidermoid carcinoma (A431) cell lines, as well as on some common bacteria, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Materials &amp; Methods: Initially, myrtle EO was analyzed using Gas Chromatography-Mass Spectrometry. Subsequently, alginate nanoparticles were prepared via the ionic-gelation method and characterized by dynamic light scattering, Zeta potential, and attenuated total reflectance-Fourier transform infrared spectroscopy. Encapsulation efficacy was then determined using UV-Vis spectrometry. Both cytotoxicity assessment (MTT assay) and evaluation of antibacterial effects (microdilution assays) were conducted using the 96-well plate format. Results: The major compounds identified in myrtle EO were α-pinene, 1,8-cineole, linalool, linalool acetate, and geranyl acetate. The alginate nanoparticles exhibited a size of 160 ± 9 nm, a SPAN of 0.96, and a Zeta potential of -26 ± 2 mV. The encapsulation efficacy was determined to be 78.4%. It was found that the nanoparticles demonstrated cytotoxicity against A375 and A431 cells with IC50 values of 211 μg/mL and 308 μg/mL, respectively. The most potent antibacterial effect was observed against S. aureus (IC50: 266 μg/mL). Conclusion: The alginate nanoparticles containing myrtle EO, which exhibited notable cytotoxicity against melanoma and epidermoid carcinoma cells as well as potent antibacterial effects, show promise for further investigation in vivo studies.

Exploring the anticancer potential of new 3-cyanopyridine derivatives bearing N-acylhydrazone motif: Synthesis, DFT calculations, cytotoxic evaluation, molecular modeling, and antioxidant properties.

3-Cyanopyridine derivatives are known for exhibiting excellent anticancer activity due to their strong capability to inhibit various biological targets, including Pim-1 kinase, survivin, and tubulin polymerization. On the other hand, N-acylhydrazones (NAH) are known to be a very versatile motif in medicinal chemistry and drug design. Based on these data, we report in this paper, the synthesis of novel 3-cyanopyridines incorporating N-acyl hydrazine scaffold, the evaluation of their cytotoxicity on the breast (MCF-7) and ovarian (A-2780) cancer cell lines and their antioxidant properties. Excluding 4a and 4d, all tested molecules exhibited high cytotoxicity against A-2780, with IC50 values ranging from 1.14 to 1.76 µM. Conversely, only four molecules 3d, 4b, 4c, and 4d demonstrated cytotoxicity against MCF-7, with IC50 values ranging from 1.14 to 3.38 µM. On the other hand, all the tested molecules exhibited a moderate antioxidant capacity in both the DPPH and metal chelation assays. Docking and molecular dynamics studies revealed that 2d, 3d, and 4d are potential inhibitors of tubulin and the œstrogen receptor, which may explain their high cytotoxicity. These results are promising to study these newly synthesized 3-cyanopyridine-N-acylhydrazones in depth for use as potential anticancer candidates.

Exploring the Iris haynei essential oil: analysis of phytochemical composition, evaluation of cytotoxicity, antimicrobial properties, and AMPA receptor modulation

BackgroundThe complex composition of essential oils (EOs) derived from plants offers potential therapeutic approaches for treating various medical conditions, including neurological disorders and infectious diseases. This research aimed to comprehensively analyze the phytochemical composition of Iris haynei EO and evaluate its pharmacological properties, specifically its cytotoxicity, antimicrobial activity, and modulation of AMPA receptors.ResultsThe analysis of I. haynei EO, conducted using gas chromatography and mass spectroscopy, identified diethyl phthalate, α-terpineol, and benzyl acetate as the main components. Cytotoxicity experiments on several cancer cell lines revealed a dose-dependent impact. Electrophysiological recordings on HEK293T cells expressing AMPARs showed varying levels of inhibition across different subunits, with receptors encoding GluA2 exhibiting the most significant effects. The EO also demonstrated significant antibacterial activity against both Gram-positive and Gram-negative bacteria, as well as fungi.ConclusionsThe findings of this study underscore the potential therapeutic benefits of I. haynei EO, particularly in treating neurological conditions associated with AMPA receptor dysfunction and exhibiting antimicrobial activity against infectious agents. The promising results warrant further investigation into the pharmacological effects of the EO, suggesting a novel approach for addressing cerebral ischemia and related neurological diseases.Graphical

Optimal development of apoptotic cells-mimicking liposomes targeting macrophages

Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Multifunctional engineering of Mangifera indica L. peel extract-modified bacterial cellulose hydrogel: Unveiling novel strategies for enhanced heavy metal sequestration and cytotoxicity evaluation

The escalating interest in bacterial cellulose (BC) confronts a substantial obstacle due to its biologically inert properties. Hence, BC was modified with ethanolic mango peel extract (EEMP) for various industrial and medical applications of the novel nanocomposite (BC/EEMP). High-performance liquid chromatography (HPLC) delineated the phenolic composition of EEMP, revealing a repertoire of polyphenolic compounds, notably chlorogenic acid, gallic acid, catechin, and ellagic acid. EEMP exhibited broad-spectrum antimicrobial activity against Candida albicans and Staphylococcus aureus, with MIC of 0.018 mg/mL and 0.009 mg/mL, respectively. The removal mechanism of Pb2+ and Ni2+ by BC/EEMP nanocomposite membrane via SEM, EDX, FT-IR, and XRD was characterized, indicating deposition and aggregation of heavy metals with diminished porosity. Heavy metal removal optimization using the Box-Behnken design achieved maximal removal of 95.5 % and 90 % for Pb2+ and Ni2+, respectively. Moreover, BC/EEMP nanocomposite demonstrated selective dose-dependent anticancer activity toward hepatoma (HepG-2, IC50 of 208.8 μg/mL), skin carcinoma (A431, IC50 of 216.7 μg/mL), and breast carcinoma (MDA, IC50 of 197.5 μg/mL), attributed to the enhanced availability of biologically active polyphenolic compounds and physical characteristics of BC. This study underscores the remarkable potential of BC/EEMP nanocomposite for multifaceted industrial and biomedical applications, marking a pioneering contribution to the field.

Synthesis, Characterization, and Cytotoxicity Evaluation of Chlorambucil-Functionalized Mesoporous Silica Nanoparticles.

This study describes the synthesis and characterization of chlorambucil (CLB)-functionalized mesoporous silica nanoparticles (MSNs) for potential application in cancer therapy. The nanoparticles were designed with a diameter between 20 and 50 nm to optimize cellular uptake and avoid rapid clearance from the bloodstream. The synthesis method involved modifying a previously reported technique to reduce particle size. Successful functionalization with CLB was confirmed through various techniques, including Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The cytotoxicity of the CLB-functionalized nanoparticles (MSN@NH2-CLB) was evaluated against human lung adenocarcinoma cells (A549) and colon carcinoma cells (CT26WT). The results suggest significantly higher cytotoxicity of MSN@NH2-CLB compared to unbound CLB, with improved selectivity towards cancer cells over normal cells. This suggests that MSN@NH2-CLB holds promise as a drug delivery system for targeted cancer therapy.

Application and Cytotoxicity Evaluation of Fe-MIL-101 Nanozyme in Milk.

In this study, we used Fe-MIL-101 nanozyme to convert lactose into lactitol, and it was proved that Fe-MIL-101 nanozyme has lactase-like activity. Due to the potential health effects of nanomaterials, we evaluated the cytotoxicity of Fe-MIL-101 nanozyme. To reduce the potential toxicity of the nanozyme, we applied centrifugation and membrane filtration. When the membrane aperture size was 100nm, the residual content of Fe-MIL-101 nanozyme was 14.09μg/mL. The residual content of Fe-MIL-101 nanozyme was reduced by optimizing time, temperature, and Fe-MIL-101 nanozyme-to-substrate ratio. It was showed that the concentration of Fe was 38.47mg/kg and the concentration of H2BDC was 0mg/kg under optimized conditions (110℃, 2h of reaction and the ratio of Fe-MIL-101 nanozyme to substrate is 1:20). The result met the national standard of China. Experiments measuring cytotoxicity, oxidative stress, and cell membrane damage revealed that less than 20μg/mL Fe-MIL-101 nanozyme had no significant cytotoxicity. Our study findings showed that Fe-MIL-101 nanozyme reduced lactose content in milk.

Synthesis, in vitro and in silico evaluation of gallamide and selenogallamide derivatives as inhibitors of the SARS-CoV-2 main protease.

The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against Mpro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds 3a, 3b, and 3f showed the highest enzymatic inhibition with IC50 = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide 6a exhibited IC50 values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener 3c shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds 3e and 3g, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC50 > 150 µM. Derivative 3d showed moderate cytotoxicity against both cell lines, whereas 6d was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds 3a, 3b, and 3f show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.

Synthesis and biological evaluation of novel 3,6- amide and thioamide substituted- 2,3,4,9-tetrahydro-1H-carbazoles for anti-cancer activity

Herein, we report the synthesis of new compounds with demonstrated anticancer properties based on the 2,3,4,9-tetrahydro-1H-carbazole scaffold. The Fischer indolization method was used to close the heterocyclic motif. The synthesis method's scope and limitations were thoroughly assessed through a series of experiments. Biological assays revealed that two thioamide compounds exhibited significant anticancer activity against MCF-7, HTC116, and A596 cell lines. Comprehensive in vitro profiling included evaluation of cell cytotoxicity, morphological alterations, colony formation and cell adhesion in 3D cultures, cell cycle analysis, DNA damage induction, impact on mitochondria, and apoptosis. Ex ovo studies further demonstrated these compounds' potential to inhibit angiogenic processes. Our results indicate that the newly developed compounds activate processes leading to DNA damage and disruption of mitochondrial function.