Cytotoxicity Studies Research Articles

Synthesis, Antioxidant and Cytotoxic Activity Studies of 2-Chlorobenzo[h]quinoline containing 2,4,5-Trisubstituted Imidazole Derivatives

Synthesis, Antioxidant and Cytotoxic Activity Studies of 2-Chlorobenzo[h]quinoline containing 2,4,5-Trisubstituted Imidazole Derivatives

Polymeric liposomes of emtricitabine employing modified pullulan—an attempt to reduce associated hepatotoxicity

Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and in vitro and ex vivo drug release. An in vivo study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. The in vitro and ex vivo drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib.

Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4- to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility-lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.

A series of pyrimidine-based antifungals with anti-mold activity disrupt ER function in Aspergillus fumigatus.

Fungal infections are a major contributor to morbidity and mortality among immunocompromised populations. Moreover, fungal disease caused by molds are difficult to treat and are associated with particularly high mortality. To address the need for new mold-active antifungal drugs, we performed a high-throughput screen with Aspergillus fumigatus, the most common pathogenic mold. We identified a novel, pyrimidine-based chemical scaffold with broad-spectrum antifungal activity including activity against several difficult-to-treat molds. A chemical genetics screen of Saccharomyces cerevisiae suggested that this compound may target the endoplasmic reticulum (ER) and perturb ER function and/or homeostasis. Consistent with this model, this compound induces the unfolded protein response and inhibits secretion of A. fumigatus collagenases. Initial cytotoxicity and pharmacokinetic studies show favorable features including limited mammalian cell toxicity and bioavailability in vivo. Together, these data support the further medicinal chemistry and pre-clinical development of this pyrimidine scaffold toward more effective treatments for life-threatening invasive mold infections.IMPORTANCEInvasive fungal diseases are life-threatening infections caused by fungi in immunocompromised individuals. Currently, there are only three major classes of antifungal drugs available to treat fungal infections; however, these options are becoming even more limited with the global emergence of antifungal drug resistance. To address the need for new antifungal therapies, we performed a screen of chemical compounds and identified a novel molecule with antifungal activity. Initial characterization of this compound shows drug-like features and broad-spectrum activity against medically important fungi. Together, our results support the continued development of this compound as a potential future therapy for these devastating fungal infections.

Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/RACV) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β-D-ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased.

Anastrozole and Paclitaxel Loaded Nanocrystals: Evaluation of Anticancer Activity

To study the cytotoxic study of anastrozole and paclitaxel-loaded nanocrystals on MDA-MB-231 cell lines for enhanced anticancer activity. Paclitaxel is a tubulin-targeting cytoskeletal drug that interferes with microtubule structures, and anastrozole’s mechanism of action is apoptosis in living cells. Methylthiazol tetrazolium (MTT) assay was used to determine anticancer activity. After 24 hours of treatment, the highest ALN and PLN concentrations (100 μg/mL) showed a cytotoxic effect. The inhibition rate of doxorubicin (standard) was found at 24 hours with 89.6. The viability values of Anastrozole loaded nanocrystals (ALN) were 14.03 (100), 22.76 (80), 28.23 (40), 34.9 (20), 40.26 (10), 50.13 (5), 60.53 (2), 80.66 (1), and 99.11 (0) μg/mL. When compared to the standard, viability was 38.23% and drug unloaded nanocrystal was 86.06% (100 μg/mL) 24 hours after anastrozole (100 μg/mL) administration to MDA-MB-231 cells. All experimental groups showed significantly from the control group. The cytotoxicity effect was determined with low dose of anastrozole and paclitaxel-loaded nanocrystals. The cell viability and toxic effects of the ALN and PLN also tested. As ALN and PLN concentrations grew, so did the harmful effect on MDA-MB-231 cell viability. Cell count was significantly reduced (p < 0.05) at high ALN and PLN concentrations (100 μg/mL). Finally, the MTT assay revealed that ALN and PLN cytotoxic to MDA- MB-231. Exposure to dose-dependently hazardous doses of ALN and PLN nanocrystal formulations resulted in increased nuclear intensity, cytochrome c, and permeability of the cell membrane in the MDA-MB-231 cell line.

Synthesis, structure and biological properties of the zinc(II) complexes with 5-(4-chlorophenyl)-1H-tetrazole and oligopyridine derivatives

In this work, we present six new zinc(II) complexes with the general formulas [Zn2(oligopyridine)2L4] and [Zn(oligopyridine)2L2], where L– = 5-(4-chlorophenyl)-1H-tetrazolate anion, and oligopyridine = 1,10-phenanthroline or 2,2′-bipyridine derivatives (dmphen – 4,7-dimethyl-1,10-phenanthroline, phen – 1,10 phenanthroline, dmbipy – 2,2′-bi-4-picoline, bipy – 2,2′-bipyridine), which have been synthesized with high yield and characterized by IR spectroscopy, elemental, thermogravimetric, single crystal and powder X-ray analyses. A distorted square-pyramidal and octahedral geometry of zinc(II) ion have been demonstrated by single crystal X-ray diffraction analysis. The tetrazolate ligand exhibits two types of coordination: monodentate, and bidentate-bridging via the N(2), N(3) or N(1), N(2) atoms. The behavior of all complexes in solution has been investigated by UV–Vis and the 1H, 13C NMR spectroscopy, conductometry, and mass spectrometry. The antimicrobial study of the compounds has been carried out against E. coli, St. aureus, P. italicum, and C. steinii, and [Zn2(dmbipy)2L4] has been shown to possess significant protistocidal properties. According to the cytotoxicity study,all complexes don’t have cytotoxic properties in 1–100 µM concentration range against tumor human cell lines (larynx carcinoma Hep2, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7) with the exception of complex 5 which has displayed significant cytotoxic effect (LC50 = 19.8 ± 2.4 μM) against Hep2 cells. However, obtained compounds have a pronounced cytostatic effect on all tumor cell lines.

Ergosterol and its metabolites as agonists of Liver X receptor and their anticancer potential in colorectal cancer

Aberrant cholesterol homeostasis is a well-recognized hallmark of cancer and is implicated in metastasis as well as chemotherapeutic resistance, the two major causes of cancer associated mortality. Liver X receptors (LXRs) are the key transcription factors that induce cholesterol efflux via enhancing the expression of ABCA1 and ABCG1. Therefore, a comprehensive analysis of several novel sterols namely ergosta-7,22,24(28)-trien-3β-ol (Erg1), ergosta-5,22,25-trien-3-ol (Erg2), ergosta-5,7,22,24(28)-tetraen-3β-ol (Erg3), and ergosta-7,22-dien-3β-ol (Erg4) as LXR agonists has been performed. Molecular docking studies have shown that these sterols possess higher binding affinities for LXRs as compared to the reference ligands (GW3965 and TO901317) and also formed critical activating interactions. Molecular dynamic (MD) simulations further confirmed that docking complexes made of these sterols possess significant stability. To assess the extent of LXR activation, ABCA1 promoter was cloned into luciferase reporter plasmid and transfected into HCT116 cells. It was observed that treatment with Erg, Erg2 and Erg4 led to a significant LXR activation with an EC50 of 5.64 µM, 4.83 and 3.03 µM respectively. Furthermore, a significant increase in mRNA expression of NR1H2 and LXR target genes i.e. ABCA1, ABCG1 and ApoE was observed upon Erg treatment. Flow cytometric analysis have revealed a significant increase in the accumulation of ABCA1 upon Erg treatment. Cytotoxicity studies conducted on colorectal cancer cell and normal epithelial cell line showed that these sterols are selectively toxic towards cancer cells. Taken together, our findings suggests that ergosterol activates LXRs, have significant anticancer activity and could be a likely candidate to manage aberrant cholesterol homeostasis.

Bis‐Ureido‐Substituted Benzenesulfonamides: Evaluation of Their Antibacterial, Anticholinesterase, and Cytotoxicity Properties

AbstractIn this study, we present the re‐synthesis of a series of twelve bis‐ureido‐substituted benzenesulfonamides, focusing on their potential as antibacterial, anticholinesterase, and cytotoxic agents. First, the antibacterial assessment of these compounds indicated varying activity levels across different bacterial strains, with S. aureus displaying resistance to all compounds, while compounds 9 and 11 exhibited promise against E. faecalis with a MIC value of 31.25 μg/mL. Additionally, P. aeruginosa showed resistance to compounds containing 4‐aminobenzene sulfonamides, whereas derivatives such as (8–11) and compound 19 displayed notable activity against E. coli, comparable to Ampicillin. Second, their anticholinesterase activities were examined, with a focus on their potential role in addressing neurological disorders, particularly Alzheimer′s disease. The findings indicated that all synthesized compounds showed a significant inhibitory effect on both AChE and BChE enzymes. Compound 11 demonstrated the most effective inhibition on the AChE enzyme with an IC50 value of 0.2160±0.09 nM, while compound 18 exhibited the most potent inhibition on the BChE enzyme with an IC50 value of 0.2257±0.06 nM. Finally, cytotoxicity studies were conducted across various cell lines, including breast, lung, and prostate cancer cells and normal cells. The results revealed that compound 12 emerged as the most potent tested compound against breast cancer cells with no cytotoxic effect on CRL‐4010 normal breast epithelial cells. The research presented here not only highlights the multifaceted pharmacological potential of bis‐ureido‐substituted benzenesulfonamides, but also indicates their potential as versatile compounds for antibacterial, anticholinesterase, and cytotoxicity applications, opening up new avenues for drug discovery and development.

HGG-18. ONC201 COMBINED WITH THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD AS A NEW THERAPEUTIC REGIME FOR PEDIATRIC HIGH-GRADE AND DIFFUSE MIDLINE GLIOMAS

Abstract BACKGROUND Pediatric high-grade (pHGGs) and diffuse midline gliomas (DMGs) patients have the worst survival rates in childhood cancer. The oncolytic adenovirus Delta-24-RGD and the imipridone ONC201 are two of the most promising therapeutic agents in the field, having demonstrated safety and effectiveness in clinical trials. Therefore, we evaluated whether the Delta-24-RGD/ONC201 combination could increase the therapeutic benefit in pHGGs and DMGs. METHODS A battery of human pHGG, DMG, and murine DMG cell lines was used for the study. Viral replication was assessed by hexon titration. Characterization of combination response was assessed by MTS, RNAseq, Seahorse, and immunofluorescence. In vivo experiments were performed to assess the efficacy of the proposed combination. The tumor microenvironment infiltration was evaluated by flow cytometry. RESULTS ONC201 cotreatment with Delta-24-RGD did not affect the virus replication capability in vitro. Cytotoxicity studies showed that cotreatment was either synergistic or additive. Importantly, cells treated with the combination maintain the mitochondrial damage caused by ONC201, showed a significant reduction of IGF1/IGF1R and PDGF pathways, and increased nuclear DNA damage. Remarkably, Delta-24-RGD/ONC201 treatment in human pHGG and DMG xenograft-bearing mice showed a safe toxicity profile and a significant increase in the median overall survival compared to each agent alone. Combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment towards a proinflammatory phenotype. We observed an increase in both lymphoid and myeloid lineage in the combined treatment versus either single treatment. Interestingly, Delta-24-RGD/ONC201 produces a higher activation in CD8+ T cells, higher activation and proliferation in CD4+ T cells, and less immunosuppressed regulatory T cells. CONCLUSIONS Our data supports that the Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone by potentiating nuclear DNA damage and improving the antitumor (immune) response. Altogether, our results reveal the potential of this combination for future clinical trials.

Biocorrosion and Cytotoxicity Studies on Biodegradable Mg-Based Multicomponent Alloys.

Magnesium-based multicomponent alloys with different compositions, namely Mg60Al20Zn5Cu10Mn5 (Mg60 alloy), Mg70Al15Zn5Cu5Mn5 (Mg70 alloy), and Mg80Al5Cu5Mn5Zn5 (Mg 80) alloys, were prepared using the disintegrated melt deposition technique. The DMD technique is a distinctive method that merges the benefits from gravity die casting and spray forming. This approach facilitates high solidification rates, process yields, and reduced metal wastage, resulting in materials with a fine microstructure and minimal porosity. Their potential as biodegradable materials was assessed through corrosion in different simulated body fluids (SBFs), microstructure, and cytotoxicity tests. It was observed that the Mg60 alloy exhibited low corrosion rates (~× 10-5 mm/year) in all SBF solutions, with a minor amount of corrosive products, and cracks were observed. This can be attributed to the formation of the Mg32(AlZn)49 phase and to its stability due to Mg(OH)2 film, leading to excellent corrosion resistance when compared to the Mg70 and M80 alloys. Conversely, the Mg80 alloy exhibited high corrosion rates, along with more surface degradation and cracks, due to active intermetallic phases, such as Al6Mn, Al2CuMg, and Al2Cu phases. The order of corrosion resistance for the Mg alloy was found to be ASS > HBSS > ABP > PBS. Further, in vitro cytotoxicity studies were carried out using MDA-MB-231 tumor cells. By comparing all three alloys, in terms of proliferation and vitality, the Mg80 alloy emerged as a promising material for implants, with potential antitumor activity.

Triazole-benzenesulfonamide hybrids: Synthesis, biological evaluation, and molecular docking study as non-toxic antimicrobial and antioxidant agents

We have synthesized a library of twenty novel heterocyclic compounds having benzenesulfonamide and triazole moieties in their skeleton. Synthesized target compounds were tested for their inhibition potential against the growth of seven bacterial and one fungal pathogens. Free radical scavenging activities were also determined for the synthesized series of compounds using DPPH method. Furthermore, cytotoxicity studies of the target compounds were performed against mouse fibroblast animal cell lines and plant seed germination cell lines. To identify the binding modes, molecular docking of the most active antibacterial compound 3e and the most active antifungal compound 3g was performed in the active sites of target enzymes. All the tested compounds were found to be good antibacterial (MIC values = 4.9 – 37.8 µM) and antifungal (MIC values = 5.4 – 37.8 µM) agents. Results of antioxidant study showed that all the tested compounds are moderate to excellent free radical scavengers (% RSA values = 75.45 – 95.34). Furthermore, all were found safe against both the tested cell lines during cytotoxicity studies.

Biofabrication of Centella asiatica mediated metal (Silver and Iron) nanoparticles and their enhanced antimicrobial, anticancer activity in retinoblastoma Y79 cancer cells

In recent years, metallic nanoparticles have played a significant role in nanotechnology and bio fabrication, being considered an alternative to antibiotics due to their feasibility for use in both bacterial detection and infection prevention. Moreover, recent studies have demonstrated the green process of developing nanoparticles with anticancer activity against many human cancer cell lines. In the current investigation, the biogenic synthesis of silver and iron nanoparticles using the aqueous leaf extract of Centella asiatica was performed. The leaf extracts underwent characterization for antioxidant activity, TLC analysis, phytochemical analysis, and GC-MS analysis of Centella asiatica. The leaf extracts revealed the antioxidant potential of the phytoconstituents, namely phenolic and flavonoid contents, responsible for the anticancer activity. The synthesized silver and iron nanoparticles were analysed using various techniques, including UV-Vis absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy with energy-dispersive spectroscopy, and transmission electron microscopy. Confirmation of silver and iron nanoparticle formation was achieved through UV-Vis absorption spectra, showing absorption peaks at 362 nm and 342 nm, respectively. Fourier transform infrared spectroscopy analysis confirmed the biological moieties involved in synthesis and stability. X-ray diffraction (XRD) analysis verified the crystallinity of the nanomaterials, while scanning electron microscopy depicted spherical shapes for silver nanoparticles and similarly round shapes for iron nanoparticles. EDS analysis revealed 87.12 % silver and 40.12 % iron content in the respective nanoparticles. TEM imaging displayed predominantly spherical silver nanoparticles, sized at 50 nm. The antimicrobial efficacy of the biosynthesized silver and iron nanoparticles was evaluated using the well diffusion method, along with the determination of the minimum inhibitory concentration. Results indicated moderate effectiveness of silver nanoparticles against Escherichia coli (7±0.036) and Aspergillus niger (5±0.034) compared to iron nanoparticles. The minimum inhibitory concentrations against Staphylococcus aureus were 46.51–86.74 % for silver nanoparticles and 42.79–77.44 % for iron nanoparticles. The anticancer effect was evaluated using human retinoblastoma (Y79) cell lines. The cytotoxicity study using the MTT assay revealed that Centella asiatica-mediated silver nanoparticles exhibited significant cytotoxicity to human retinoblastoma cells, with a low IC50 value of 49.56 μg/ml. Based on the results, it is feasible to infer that biofabricated nanoparticles could potentially serve as antibacterial and antifungal compounds. Furthermore, the synthesized silver nanoparticles, followed by iron nanoparticles, showed high effectiveness against human retinoblastoma cancer cells, indicating potential for future drug discovery to inhibit retinoblastoma cancer for biomedical applications.

The combination therapy using tyrosine kinase receptors inhibitors and repurposed drugs to target patient-derived glioblastoma stem cells

The lesson from many studies investigating the efficacy of targeted therapy in glioblastoma (GBM) showed that a future perspective should be focused on combining multiple target treatments. Our research aimed to assess the efficacy of drug combinations against glioblastoma stem cells (GSCs). Patient-derived cells U3042, U3009, and U3039 were obtained from the Human Glioblastoma Cell Culture resource. Additionally, the study was conducted on a GBM commercial U251 cell line. Gene expression analysis related to receptor tyrosine kinases (RTKs), stem cell markers and genes associated with significant molecular targets was performed, and selected proteins encoded by these genes were assessed using the immunofluorescence and flow cytometry methods. The cytotoxicity studies were preceded by analyzing the expression of specific proteins that serve as targets for selected drugs. The cytotoxicity study using the MTS assay was conducted to evaluate the effects of selected drugs/candidates in monotherapy and combinations. The most cytotoxic compounds for U3042 cells were Disulfiram combined with Copper gluconate (DSF/Cu), Dacomitinib, and Foretinib with IC50 values of 52.37 nM, 4.38 µM, and 4.54 µM after 24 h incubation, respectively. Interactions were assessed using SynergyFinder Plus software. The analysis enabled the identification of the most effective drug combinations against patient-derived GSCs. Our findings indicate that the most promising drug combinations are Dacomitinib and Foretinib, Dacomitinib and DSF/Cu, and Foretinib and AZD3759. Since most tested combinations have not been previously examined against glioblastoma stem-like cells, these results can shed new light on designing the therapeutic approach to target the GSC population.

Phytochemical Screening, GC-MS Analysis, and Evaluation of Antioxidants, Cytotoxicity, Analgesic, and Anti-Diarrheal Activity of the Extracts of the Leaves of Syzygium reticulatum Wight Walp

Syzygium genus is extensively used in managing different diseases such as antimicrobial, anti-diarrheal, antidiabetic, analgesic, anti-inflammatory, antioxidant, and anticancer activities. The present study aims to investigate phytochemicals by screening tests and GC-MS analysis and evaluate the antioxidants, cytotoxicity, analgesic, and anti-diarrheal activity of the extracts of the leaves of Syzygium reticulatum. The leaves of the S. reticulatum were extracted with hexane and methanol by the maceration process successively, denoted as SRH and SRM. The extract’s phytochemical analyses found flavonoids, alkaloids, saponins, tannins, glycosides, and carbohydrates. The GC-MS analysis of the methanol extract identified 8 compounds. The major components were identified as Diisooctyl phthalate (96.903 %), 2-methyltetracosane (1.094 %), and others with fewer amounts. The result of the antioxidant study of the extracts as total phenolic content of SRH 8.92 ± 0.62 and SRM 340.107 ± 11.11 mg/g, respectively, total flavonoids content of SRH 7.85 ± 0.71 and SRM 105.16 ± 0.93 mg/g, IC50 values of the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay of SRM was 14.67 µg/mL, SRH was 41.26 µg/mL and ascorbic acid 14.08 µg/mL; the total antioxidant capacity of SRH was 21.33 ± 2.52 mg/g, whereas SRM was 353.71 ± 4.59 mg/g. The results of these studies suggest that methanol extract has a more potent antioxidant capacity than hexane extract. The methanol extract also exhibited higher toxicity (LC50 value 49.99 µg/mL) compared to hexane extract (LC50 value 370.348 µg/mL), as revealed by the Brine shrimp nauplii cytotoxic study. An analgesic study of the methanol extract found that a lower dose (250 mg/kg) has more significant analgesic activity than the higher dose and standard drug aspirin. At 90 min, the hot plate’s highest percentage of latency elongation was 110.32, while the acetic acid-induced writhing inhibition was 63.04 %. At a dose of 500 mg/kg, the methanol extract also shown good efficacy in mice suffering from castor oil and magnesium sulfate-induced diarrhea. The findings from the study of the leaves of the S. reticulatum exhibited that methanol extracts have significant antioxidant, cytotoxic, analgesic, and anti-diarrheal activity. HIGHLIGHTS The extract’s phytochemical analyses found flavonoids, alkaloids, saponins, tannins, glycosides, and carbohydrates The GC-MS analysis of the methanol extract identified 8 compounds. The major components were identified as Diisooctyl phthalate (96.903 %), 2-methyltetracosane (1.094 %) The antioxidant and cytotoxicity studies suggest that methanol extract has a more potent antioxidant and cytotoxic capacity than hexane extract The findings from in-vivo study of the leaves of the reticulatum also exhibited that methanol extracts have significant analgesic, and anti-diarrheal activity GRAPHICAL ABSTRACT

Naphthalimide-based light-induced nitric oxide-releasing nanoscale vesicles with visual detection and cytotoxicity studies

The therapeutic potential of nitric oxide (NO) has been receiving increasing interest, but achieving controlled release under physiological conditions remains challenging. Herein, we report a colorimetric and fluorescence responsive naphthalimide-based amphiphilic N-nitroso-based NO donor (Nap-NO) and its NO-releasing behavior. Nap-NO was incorporated into phospholipid nanovesicles to make it biocompatible and water-soluble. Light-induced NO-releasing behavior and emission changes were monitored via UV-vis, colorimetric detection, IR (Infrared) spectroscopy studies, and Griess assay. The Nap-NO donor within the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-cholesterol vesicles exhibited a slower release rate, with a significantly extended half-life as compared to the only DOPC vesicles. Incorporating the Nap-NO into alginate hydrogel beads enables a simple, visual detection of NO release through color and emission changes. Bioimaging experiments within the HCT cell line reveal the use of the new NO donor for fluorescent bio-imaging and clearly illustrate their proficiency in killing cancer cells upon NO delivery in the presence of light.

Magnetic bio-composite based on zirconium and chitosan modified activated carbon from peanut husk with enhanced antibacterial and adsorptive potential for alizarin red and congo red in wastewater

Creating new adsorbents is crucial for removing contaminants from water due to increased industrialization, which has worsened water pollution in recent years. In this study, a magnetic biocomposite, Zirconium (Zr)-doped chitosan (CS)-coated iron oxide nanoparticles (Fe3O4-NPs)-peanut husk (PH)-based activated carbon (AC) (Zr-CS/Fe3O4-NPs@PH-AC), was synthesized for efficient removal of alizarin red (AR) and congo red (CR) dyes, alongside antibacterial applications. Characterization via scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) analysis revealed micropores and mesopores development due to chemical activation of PH biomaterial and Fe3O4-NPs addition. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) identified functional groups and structural properties. Vibrating sample magnetometry (VSM) analyzed magnetic properties. Optimal conditions for AR/CR removal were determined, including Zr-CS/Fe3O4-NPs@PH-AC dose, dye dose, contact time, and temperature, achieving maximum removal percentages. Experimentally determined maximum adsorption capacities for AR and CR were 374.3 and 154.1 mg·g−1, respectively. Cytotoxicity studies affirmed the eco-friendly and non-toxic nature of the adsorbent by exhibiting the reduction in the cell viability from 100 % to 88.68 % from the 0 to 200 μg·L−1 respectively. Additionally, the biocomposite exhibited significant antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) due to magnetic NPs. The material in this study shows extreme compatibility for numerous applications.

Molybdenum (VI) Complexes and their Dual Role as Antidiabetic and Anticancer Agents

AbstractTwo molybdenum complexes, MoHL1 and MoHL2, are prepared from the corresponding tetradentate salen type (ONNO) ligands, HL1 and HL2, obtained from 3, 5‐dichloro salicylaldehyde, and substituted o‐phenylenediamines. The complexes are characterized by 1H NMR, FTIR, HRMS, and UV‐visible spectral techniques. The DFT studies provide insight into their structural parameters. The band gap energy and molecular orbital energies influence the charge transfer interactions within the molecule. Further, the complexes are assessed for their antioxidant efficacy, α–amylase inhibitory potential, binding propensity with deoxyribonucleic acid, and cytotoxicity studies against breast cancer cell line, MCF7. The DPPH assay demonstrates high radical scavenging ability, as evidenced by the IC50 value of 133.85±1.18 μg/mL, higher than ascorbic acid. From the results of α–amylase inhibitory assay, MoHL1 shows good inhibitory action with the IC50 value of 32.72±2.49 μg/mL higher than that of the standard acarbose. The absorption titration method, to track the binding interactions of the metal complexes with DNA, shows a marked hyperchromic effect indicating preferential binding of the complexes to the grooves of DNA helical structure. MoHL2 exerts higher cytotoxicity against cancer cell lines than MoHL1. Thus, the complexes have the potential to be developed as antidiabetic and anticancer agents.

Dual approach: micellar delivery of chlorambucil prodrug with concurrent glutathione depletion and GST inhibition for enhanced anticancer activity

Although chlorambucil (CHL) is a long-established anticancer drug, the drug failure of CHL, mediated by the intracellular defense system consisting of glutathione (GSH) and GSH S-transferase pi (GST-pi), has significantly limited the application of CHL. To overcome this issue, we first designed a GSH-responsive small-molecule prodrug (EA-SS-CHL) by combining CHL and ethacrynic acid (EA). Subsequently, drug-loaded nanoparticles (ECPP) were formed by the self-assembly between EA-SS-CHL and amphiphilic PEG-PDLLA to improve the water solubility of the prodrug and its ability to target tumor sites. Upon exposure to high intracellular GSH concentration, EA-SS-CHL gradually degrades, leading to the release of EA and CHL. The presence of EA facilitates the depletion of GSH and inhibition of GST-pi, ultimately attenuating the detoxification of the intracellular defense system to CHL. Cytotoxicity studies and apoptosis assays demonstrate that ECPP exhibits higher therapeutic efficiency than CHL. Additionally, in vivo tumor suppression effects and biocompatibility provide further evidence for the superiority of ECPP. This work presents a promising strategy to enhance the efficacy of CHL in cancer therapy.

Effect of Trastuzumab and Lonidamine‐Loaded Lipid Nanoparticles (LNP) on HER2+ Breast Cancer

AbstractOur study involves inhibition of glycolysis and inhibition of the HER2 pathway, which is highly expressed in many types of cancer. Decreased survival, negative metastasis, and induced apoptosis are expected due to the combined inhibition of these two targets. Trastuzumab was used as the HER2 inhibitor and lonidamine was used as the HK2 inhibitor. Lonidamine (LND) was delivered to cells as hybrid nanoparticles to enhance the effect of lonidamine and make it target specific. Separate cytotoxicity studies were conducted for LND, LND‐NP and Tmab. While application of lonidamine alone gave an IC50 value of 124.6 μM, application in NP reduced the IC50 value to 44.18 μM. In addition, the combination of Tmab and LND‐NP showed synergistic effects compared to treatments alone in other analyses. On the aspect of apoptosis, this combination showed a 14‐fold increased apoptosis compared to the control group. This combination therapy can prevent drug resistance. In addition, the hybrid nanoparticle structure used will prevent the formation of toxicity as it will ensure that LND is administered to the body with less repetition. Our study aims to minimize the negative effects of the chemotherapy process by improving it with various variations in future studies.