A549 Cell Lines Research Articles

Antitumor Activity of Serine Enzyme and Crude Extracts of The Earthworm Lumbricus terrestris Against A549 Human Lung Cancer Cell Line

Background: Numerous disorders have been successfully treated with earthworms, and this has been documented in ancient texts. These invertebrates are a rich natural source of biological and pharmacological compounds with antioxidant and anticancer properties. The present study aims to isolate and partially purify serine protease from the earthworm and evaluate the cytotoxic and antitumor activities of serine protease and crude extracts of the earthworm. Methods: Lumbricus terrestris earthworms were collected and processed to prepare crude extracts, isolate, and partially purify them. The anti-tumour activity's serine enzyme was evaluated by MTT assay and Live/Dead Cell Viability Assay using A549 and NHF cell lines. Results: When the concentration was doubled, it hurt the viability of A549 and NHF cells. The IC50 values for A549cell lines were194.3 and 22.57 μg/ml for crude and serine protease, respectively. Also, the crude extract does not show cytotoxicity against the normal cell line (NHF cells). The IC50 values 391,78.61 mg/ ml, respectively, using Live/Dead Cell Viability Assay, demonstrate that an increased proportion of apoptotic cell deaths in A549 cells after treatment with crude as well as enzyme there is a significant increase in the mean count of dead cells after being treated with enzyme as well as crude the mean count was 172.7 3;127.5 in cells treated with serine enzyme and crude extract, respectively, whereas in the untreated cells, it was 33.1 reflects a significant difference when compared with treated cells with serine enzyme and crud extracts (P<0.001). Conclusion: These findings revealed that Serin enzyme and crude extract of Lumbricus terrestris possesses excellent antitumor activity.

ERK5 mediates pro-tumorigenic phenotype in non-small lung cancer cells induced by PGE2

Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting approximately 84 % of all lung cancer cases. The role of inflammation in the initiation and progression of NSCLC tumors has been the focus of extensive research. Among the various inflammatory mediators, prostaglandin E2 (PGE2) plays a pivotal role in promoting the aggressiveness of epithelial tumors through multiple mechanisms, including the stimulation of growth, evasion of apoptosis, invasion, and induction of angiogenesis. The Extracellular signal-Regulated Kinase 5 (ERK5), the last discovered member among conventional mitogen-activated protein kinases (MAPK), is implicated in cancer-associated inflammation. In this study, we explored whether ERK5 is involved in the process of tumorigenesis induced by PGE2. Using A549 and PC9 NSCLC cell lines, we found that PGE2 triggers the activation of ERK5 via the EP1 receptor. Moreover, both genetic and pharmacological inhibition of ERK5 reduced PGE2-induced proliferation, migration, invasion and stemness of A549 and PC9 cells, indicating that ERK5 plays a critical role in PGE2-induced tumorigenesis. In summary, our study underscores the pivotal role of the PGE2/EP1/ERK5 axis in driving the malignancy of NSCLC cells in vitro. Targeting this axis holds promise as a potential avenue for developing novel therapeutic strategies aimed at controlling the advancement of NSCLC.

Chemical Composition, In vitro and In silico Evaluation of Essential Oil from Ocimum tenuiflorum and Coriandrum sativum Linn for Lung Cancer.

Medicinal plants play an essential role in everyday life; plants highly contain therapeutic phytoconstituents commonly used to treat various diseases. This paper discusses the Chemical composition, In vitro antiproliferative activity and In silico study of essential oil extracted from Ocimum tenuiflorum (family Lamiaceae) and Coriandrum sativum (family Apiaceae). In present study GC-MS was used to identify the chemical constituents from O. tenuiflorum and C. sativum. In vitro antiproliferative activity was performed on A549 cancer cell lines. In silico study was performed by Schrodinger's maestro software to identify chemical constituents in both plants as potential EGFR inhibitors for the treatment of lung cancer. The essential oil was extracted by hydro distillation from aerial parts of O. tenuiflorum and C. sativum. The volatile oil sample was analyzed by (GC-MS) Gas Chromatography- Mass Spectrometry. Different chemical constituents were identified based on the retention index and compared with the NIST library. The oil samples from O. tenuiflorum and C. sativum was also evaluated for antiproliferative activity against human lung cancer A549 cell lines. In silico study was performed by Schrodinger maestro software against EGFR (PDB ID 5HG8). O. tenuiflorum essential oil contains Eugenol (42.90%), 2-β-Elemene (25.98%), β- Caryophyllene (19.12%) are the major constituents. On the other side, C. sativum contains nnonadecanol- 1 (16.37%), decanal (12.37%), dodecanal (12.27%), 2-Dodecanal (9.67%), Phytol (8.81%) as the major constituents. Both the oils have shown in vitro antiproliferative activity against human lung cancer cell lines A549 having IC50 values of 38.281 μg/ml (O. tenuiflorum) and 74.536 μg/ml (C. sativum). Molecular interactions of constituents hydro distilled from two oils was analysed by schrodinger maestro software against EGFR (PDB ID 5HG8). The oil sample extracted from O. tenuiflorum showed more antiproliferative activity than C. sativum. In silico study showed that two chemical constituents, namely di-isobutyl phthalate (-7.542 kcal/mol) and dibutyl phthalate (-7.181 kcal/mol) from O. tenuiflorum and one diethyl phthalate (-7.224 kcal/mol) from C. sativum having more docking score than standard Osimertinib which indicates the effectiveness of oils for lung cancer.

New Organoruthenium(II) Complexes Containing Andrographolide‐Appended Hydrazide Derivatives: Synthesis, Spectral Characterization, Anticancer Evaluation

ABSTRACTA new set of andrographolide‐appended hydrazide derivatives (AFC, AGC, and ATC) were prepared from the reaction of andrographolide with furan‐2‐carboxylic acid hydrazide (AFC), pyridine‐3‐carboxylic acid hydrazide (AGC), and thiophene 2‐carboxylic acid hydrazide (ATC), and their corresponding ruthenium(II) complexes (Ru‐AFC, Ru‐AGC, and Ru‐ATC) were synthesized by the direct reaction of [RuCl2(η6‐p‐cymene)]2 with ligands in dichloromethane under stirring condition. The compounds were analyzed by elemental analysis, IR, UV‐Vis, 1H NMR, and ESI‐MS spectrometric techniques, and the obtained spectral data revealed that the ligands coordinated to Ru(II) ion through their enone oxygen and amine nitrogen. Antioxidant activities of the ligands and complexes were calculated against DPPH•, ABTS•+, O2−, and NO• free radicals and their results were compared with standard antioxidants. The cytotoxic activity of the synthesized ligands and complexes toward A549 and HeLa cell lines was evaluated using MTT method (MTT = 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide). Among the compounds, the complex Ru‐AGC showed better cytotoxic effect against A549 and HeLa cancer cells with IC50 values of 4.75 ± 0.17 and 6.32 ± 0.26 μM, respectively. Further, the nontoxic nature of the compounds was confirmed by using human umbilical vein endothelial (HUVEC) cells. The apoptosis was inspected with AO/EB and DAPI staining methods; further, the percentages of the apoptotic and necrotic cells were determined by flow cytometry. Overall, the biological activities of our ruthenium(II)‐arene complexes were found to be more potent than their parent ligands due to chelation, and among the complexes, Ru‐AGC showed better activity due to the presence of pyridine ring in the N‐terminal position of the ligand. The obtained results highlighted the strong possibility to develop highly active ruthenium complexes as anticancer agents.

Impact of calcium propionate on cellular behavior in A549 and DMS114 lung cancer cell lines

Abstract Objectives To investigate the cellular and apoptotic effects of food additive calcium propionate by in vitro methods. Methods Cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, intracellular Glutathione (GSH) by luminometric method, mitochondrial membrane potential (MMP) by fluorometry, apoptosis by dual Acridine Orange/Ethidium Bromide (AO/EB) fluorescent staining were studied in lung cells. Results It has been observed that calcium propionate reduced GSH and MMP levels significantly while increased cytotoxicity, apoptosis, and reactive oxygen species (ROS) levels in both A549 and DMS114 cancer cells in a dose-dependent manner. Conclusions Cytotoxic effects of calcium propionate were more pronounced in cancer cells compared to healthy cells, suggesting its potential suitability as a chemo-preventive agent.

4-Hexylresorcinol Loaded Solid Lipid Nanoparticles for Enhancing Anticancer Activity.

Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery and cellular uptake of the drug. The purpose of this study is to encapsulate 4-HR into solid lipid nanoparticles (SLNs) to enhance its anti-cancer effect by avoiding aggregation and facilitating cellular uptake. 4-HR SLNs were prepared via hot melt homogenization with sonication. SLN characteristics were assessed by analyzing particle size, zeta potential, and drug release. Cytotoxicity, as an indicator of the anti-cancer effect, was evaluated against HeLa (cervical cancer in humans), A549 (lung cancer in humans), and CT-26 (colon carcinoma in mice) cell lines. Particle size ranged from 169.4 to 644.8 nm, and zeta potential ranged from -19.8 to -40.3 mV, which are conducive to cellular uptake. Entrapment efficiency (EE) of 4-HR was found to be 75.0-96.5%. The cytotoxicity of 4-HR-loaded SLNs demonstrated enhanced anti-cancer effects compared to pure 4-HR. The enhancement of anti-cancer effects depended on reduced particle size based on cellular uptake, the EE, and the cell type. These findings imply that 4-HR-loaded SLN is a promising strategy for chemotherapy in cancer treatment.

Rational design, synthesis and anticancer screening of 1,2,4-oxadiazole incorporated thieno[2,3-d]thiazole-isoxazole-pyridine derivatives

We have design and synthesized a new series of 1,2,4-oxadiazole incorporated thieno[2,3-d]thiazole-isoxazole-pyridine analogues (13a-j) and were confirmed by 1H NMR, 13C NMR and mass spectral data. Further, the newly synthesized compounds (13a–j) were evaluated for their preliminary anticancer activity against a panel of four human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), Colo-205 (colon cancer) & A2780 (ovarian cancer) by using of MTT method, the known chemotherapeutic agent as etoposide used as positive control. Most of the tested compounds were displayed good to moderate activities on all cell lines. The IC50 values showed compound ranges from 0.01 ± 0.009 µM to 8.41 ± 5.48 µM. Where positive control showed values range from 3.34 ± 0.152 µM to 0.17 ± 0.034 µM. Among them, compound 13a, 13b, 13c, 13d, 13e and 13f were showed more potent activity than etoposide. Predominantly, the compound 13a showed potent anticancer activity against MCF-7, A549, Colo-205, and A2780 cancer cell lines with IC50 values of 0.02 ± 0.007 µM, 0.01 ± 0.009 µM, 0.13 ± 0.052 µM, and 0.11 ± 0.083 µM.

Insights into the Theranostic Activity of Nonoxido VIV: Lysosome-Targeted Anticancer Metallodrugs.

Developing new anticancer agents can be useful, with the ability to diagnose and treat cancer worldwide. Previously, we focused on examining the effects of nonoxidovanadium(IV) complexes on insulin mimetic and cytotoxicity activity. In this study, in addition to the cytotoxic activity, we evaluated their bioimaging properties. This study investigates the synthesis of four stable nonoxido VIV complexes [VIV(L1-4)2] (1-4) using aroylhydrazone ligands (H2L1-4) and their full characterization in solid state and the solution phase stability using various physicochemical techniques. The biomolecular (DNA/HSA) interaction of the complexes was evaluated by using conventional methods. The in vitro cytotoxicity of 1-4 was studied against A549 and LN-229 cancer cell lines and found that drug 2 displayed the highest activity among the four. Since 1-4 are fluorescently active, live cell imaging was used to evaluate their cellular localization activity. Complexes specifically target the lysosome and damage lysosome integrity by producing an excessive amount (9.7-fold) of reactive oxygen species (ROS) compared to the control, which may cause cell apoptosis. Overall, this study indicates that 2 has the greatest potential for the development of multifunctional theranostic agents that combine imaging capabilities and anticancer properties of nonoxidovanadium(IV)-based metallodrugs.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 μg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Suppression of Metastasis and Angiogenesis by Taxifolin Ruthenium-p-cymene Loaded PLGA Nanoparticles in Lung Carcinoma.

Flavonoid-based organometallic complexes were revealed to be novel bioactive compounds. The taxifolin ruthenium-p-cymene nanoparticle (TaxRu-NPs) was produced in this study, and the toxicological assessment was done prior to in vivo chemotherapeutic research. Furthermore, the in vitro chemotherapeutic investigation used the A549 and NCI-H460 lung cancer cell lines. The in vitro study found that TaxRu-NPs induced apoptosis in lung cancer cells and hindered their ability to form colonies and migrate. The in vivo study showed that treatment with TaxRu-NPs restored the histological structure of a normal lung with less hyperplasia and lymphocytic infiltration. Furthermore, the treatment downregulated the angiogenic marker VEGF and the cell survival protein β-catenin and upregulated apoptotic markers like p53 and caspase-3. TaxRu-NPs treatment additionally raised the apoptotic index and decreased cancer cell growth. Finally, TaxRu-NPs effectively alleviate lung cancer by activating p53-mediated apoptosis and preventing angiogenesis and metastasis by decreasing the VEGF/β-catenin pathway.

Unveiling the antitumor synergy between pazopanib and metformin on lung cancer through suppressing p-Akt/ NF-κB/ STAT3/ PD-L1 signal pathway

Pazopanib, an inhibitor of the VEGF receptor tyrosine kinase, has demonstrated significant antitumor effects in lung cancer. However, its application as a standard treatment for this type of cancer is limited by its drug resistance and toxicity. Metformin has the potential to combat lung cancer by modifying the tumor’s immune microenvironment.In this study, we investigated the potential antitumor effects and the associated underlying molecular mechanisms of the combination of pazopanib and metformin in lung cancer. In vitro studies were conducted using the A549 and H460 lung cancer cell lines, whereas urethane-induced lung cancer-bearing mice were used for in vivo assessments. The urethane-induced mice received oral administration of pazopanib (50 mg/kg) and/or metformin (250 mg/kg) for a duration of 21 days.The results indicated that the MTT assay demonstrated a combined cytotoxic effect of the pazopanib/metformin combination in H460 and A549 cells, as evidenced by CI and DRI analyses. The observed increase in annexin V levels and the corresponding increase in Caspase-3 activity strongly suggest that this combination induced apoptosis.Furthermore, the pazopanib/metformin combination significantly inhibited the p-Akt/NF-κB/IL-6/STAT3, HIF1α/VEGF, and TLR2/TGF-β/PD-L1 pathways while also increasing CD8 expression in vivo. Immunohistochemical analysis revealed that these antitumor mechanisms were manifested by the suppression of the proliferation marker Ki67. In conclusion, these findings revealed that metformin augments the antitumor efficacy of pazopanib in lung cancer by simultaneously targeting proliferative, angiogenic, and immunogenic signaling pathways, metformin enhances the antitumor effectiveness of pazopanib in lung cancer, making it a promising therapeutic option for lung cancer.

Enhanced Photodynamic Therapy Efficacy through Solid Lipid Nanoparticle of Purpurin-18-N-Propylimide Methyl Ester for Cancer Treatment.

Photodynamic therapy (PDT) is an innovative cancer treatment that utilizes light. When light irradiates, purpurin-18-N-propylimide methyl ester (P18 N PI ME) generates reactive oxygen species that destroy cancer cells. The hydrophobic nature of P18 N PI ME presents challenges regarding its aggregation in the body, which can affect its effectiveness. This study aimed to enhance the bioavailability and effectiveness of cancer treatment by synthesizing P18 N PI ME and formulating P18 N PI ME-loaded solid lipid nanoparticles (SLNs). The efficacy of PDT was estimated using the 1,3-diphenylisobenzofuran (DPBF) assay and photocytotoxicity tests on the HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines. The P18 N PI ME-loaded SLNs demonstrated particle sizes in the range of 158.59 nm to 248.43 nm and zeta potentials in the range of -15.97 mV to -28.73 mV. These SLNs exhibited sustained release of P18 N PI ME. DPBF analysis revealed enhanced PDT effects with SLNs containing P18 N PI ME compared with standalone P18 N PI MEs. Photocytotoxicity assays indicated toxicity under light irradiation but no toxicity in the dark. Furthermore, the smallest-sized formulation exhibited the most effective photodynamic activity. These findings indicate the potential of P18 N PI ME-loaded SLNs as promising strategies for PDT in cancer therapy.

Methanolic Extract of Cimicifuga foetida Induces G1 Cell Cycle Arrest and Apoptosis and Inhibits Metastasis of Glioma Cells.

Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. Cimicifuga foetida, a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of C. foetida (CF-ME) in GBM cell lines. The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored. CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial-mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components. CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment.

In-Vitro Anti Cancer Activity Of Irinotecan & Sunitinib Loaded Nanobubbles On Selected Cell Lines.

The objective of the present research is to develop, analyze, and evaluate the cytotoxic effects of nanobubbles loaded with irinotecan and sunitinib for colorectal cancer therapy.Drug loaded dextran sulfate nanobubbles were formulated using the emulsification technique and the prepared nanobubbles were evaluated for qualitative and quantitative parameters. Cell viability MTT assay was performed to evaluate the irinotecan and sunitinib loaded nanobubblesfor cytotoxicity or ability to inhibit cell proliferation spectrophotometrically as a function of mitochondrial activity in living CR4 and A-549(irinotecan), CR4 and A-498 (sunitinib) cell lines.The irinotecan and sunitinib loaded nanobubbles were prepared successfully and the evaluated qualitative and quantitative parameters were within in the acceptable range. The in vitro anti colorectal cancer activity of irinotecanperformed on CR4 and A-549 cell lines and IC50 values are found 70.41 and 73.26 µg/ml, respectively, where activity of sunitinib performed on CR4 and A-498 cell lines and IC50 values are found to be 84.34 and 60.08 µg/ml, respectively which show excellent anticancer activity.This result concludes that the prepared irinotecan and sunitinib nanobubbles were prepared with accepted characterizations and have almost no cytotoxic effects on the CR4, A-549, A498 cell lines.

Exploring the anticancer potential of Cytotoxin 10 from Naja kaouthia venom: Mechanistic insights from breast and lung cancer cell lines

Breast and lung cancers are the leading causes of cancer-related deaths in the world. Although considerable progress has been made in the field of cancer therapy, quest to discover potent, safe and cost-effective alternatives especially from natural sources is being pursued. Snake venom, which is a treasure trove of various peptides and proteins including natural toxins that specifically target tissues and receptors in the envenomated victims. Many such proteins are being explored for their therapeutic potential against various diseases including cancers. Here, we report the mechanism of cytotoxic activity of crude venom and a purified protein, Cytotoxin from the monocled cobra (Naja kaouthia), an elapid snake with neurotoxic venom prominently found in the North-East India. The crude venom showed significant cytotoxicity against breast (MCF-7and MDA-MB-231) and lung (A549, NCI–H522) cancer cell lines. Bioassay-guided fractionation using RP-HPLC showed highest cytotoxic activity in peak P9. Liquid chromatography-tandem mass spectrometry (ESI-LC-MS/MS) analysis was employed and the fraction is identified as Cytotoxin 10 which showed comparable cytotoxicity against the experimental cell lines. Cytotoxin 10 also exhibited apoptosis in MCF-7 and A549 cell lines using AO/EtBr and flow cytometry analysis. Expressions of apoptosis related proteins e.g. Bax, Bcl-2, Caspase-7 and PARP were also studied following Cytotoxin 10 treatment in both cell lines. Molecular docking experiments performed to investigate the interactions between Cytotoxin 10 and the apoptotic proteins revealed favourable binding scores compared to their corresponding inhibitors. Interestingly, Cytotoxin 10 inhibited migration and adhesion in a time and dose-dependent manner in both MCF-7 and A549 cells. This is the first report elucidating the mechanism of cytotoxic activity of Cytotoxin 10 purified from Naja kaouthia venom of North-East India origin and could pave the way for development of potential therapeutic strategies against breast and lung cancer.

Phytochemical and Pharmacological Profile of Plants from Genus Buxus: A Review

Buxus is an evergreen shrub of the Buxaceae family. A comprehensive survey of the literature has been conducted, revealing that alkaloids are the predominant metabolites characterized by their noteworthy biological activities. Of particular interest are the alkaloids that have exhibited significant cytotoxic activity against various cell lines, including HL-60, SMMC-7721, A549, MCF- 7, SW480, ES2, and A2780 cell lines. CVB-D, buxbodine B, and buxmicrophyllines F can inhibit the growth of tumor cells and induce tumor cell apoptosis. This article reviews the chemical constituents, antitumor effect, and mechanism of Buxus alkaloids in recent years so as to provide a reference for its further development and utilization of medicinal plants of the genus Buxus.

Phytochemical, biological, and computational investigations of Ephedra alata Decne. growing in salinity conditions of Arabian Peninsula

Ephedra alata Decne is a medicinal plant widely used in traditional medicine for the management of bronchial asthma and cancer. Phytochemical analysis and biological activities, including antioxidant and anticancer effects, were investigated in the current work as new findings for the plant E. alata, a species growing wildly in the marsh and saline environments of the central area of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for the phytochemical analysis of the plant constituents. In addition, Polyphenolic profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the plant extracts were measured. Phenolic acids were found at the highest relative percentages among all the identified compounds and were measured at 66.07 mg GAE (Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest relative percentages. Mineral analysis indicated that the microelement content of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant assays revealed the ability of the plant to scavenge DPPH free radicals, reduced molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox equivalents, respectively. The extract induced transition metal chelation at 31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The plant extract inhibited the colonization and migration of cancer cells as part of its potential anticancer effects. In addition, major E. alata constituents like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the lowest binding energy to the CAIX enzyme at − 8.41, − 6.64, − 6.32, and − 6.26 kcal/mol, respectively, compared to the binding energy (− 7.72 kcal/mol) of the co-crystallized ligand (Y0R). The docking results further supported the selection of the CAIX enzyme as a standard predictive therapeutic target, since it exhibited significant binding interactions with the major constituents of the plant.

Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection

BackgroundRespiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative.MethodsThe datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties.ResultsThe study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3ʹ-azido-3ʹ-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12.ConclusionLY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection.

Novel 1,2,3-triazole derivatives containing benzoxazinone scaffold: Synthesis, docking study, DFT analysis and biological evaluation

In order to address the drastic demand for novel broad-spectrum antibacterial and anticancer medicines with enhanced activity, computer modelling was utilized to rationally develop newer anticancer triazole based drugs. A unique series of benzo[d][1,3]oxazin-4-one linked 1,2,3-triazoles was synthesised in five steps, with good yields and an assessment of their antibacterial and anticancer activities. IR spectroscopy, 1H NMR, 13C NMR, and mass spectrometry were used to characterize the synthesis of triazole compounds. From antibacterial screening, the prepared derivatives namely, 8a, 8e, 8h and 8k showed excellent inhibitory potential against S. aureus with ZI of 28 ± 0.48, 30 ± 0.42, 30 ± 0.11, 35 ± 0.23 mm respectively, compared to moxifloxacin (33 ± 0.15 mm). Compared to doxorubicin (IC50 = 2.45 ± 0.14 μM), compounds 8h and 8k demonstrated superior and exceptional cytotoxicity against the A549 cell line (IC50 = 2.30 ± 0.26 and 1.90 ± 0.30 μM, respectively). Latter All the derivatives were further subjected to in silico docking studies against human lung (PDB: 2P85), VEGFR2 kinase domain (PDB: 3CP9) and could serve as ideal leads for additional modification in the field of anticancer research. Based on docking results, 8e showed that the amino acids Arg373(A), Gly113(A), Glu103(A), Asp108(A), Ser119(A), Asn375(A), Val374(A), Lys387(A), and Asn120(A) exhibited highly stable binding to cytochrome P4502A13 receptor of lung cancer. Furthermore, Density Functional Theory (DFT) calculations are performed to support the molecular docking studies. Compounds 8e, 8h, and 8k were discovered to have estimated energy gaps (eV) of 3.181, 4.034, and 3.539 eV, respectively. Triazole 8h exhibited the lowest chemical hardness (1.962 eV) and the highest chemical softness (0.252 eV), which also suggests that it is more reactive than all the other compounds under study. Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion). In conclusion, we discovered a novel benzoxazinone linked 1,2,3-triazoles with promising antimicrobial and anticancer activity and a favorable pharmacokinetic profile.

Melanin Synthesized by the Endophytic Aureobasidium Pullulans AKW: A Multifaceted Biomolecule with Antioxidant, Wound Healing, and Selective Anti-Cancer Activity.

This study explores the potential of the endophytic fungus Aureobasidium pullulans AKW for melanin production and its anticancer activity. We report a significant achievement: A. pullulans AKW synthesized 4.89 g/l of melanin in a simple fermentation medium devoid of tyrosine, a precursor typically required for melanin biosynthesis. This suggests a potentially novel pathway for melanin production compared to previous studies relying on complex media and tyrosine. Furthermore, the isolated and characterized melanin exhibited promising selectivity as an anti-cancer agent. It triggered apoptosis in A431 cancer cells, demonstrating some selectivity compared to normal cells. This selectivity was confirmed by IC50 values and further supported by gene expression changes in A431 cells. Melanin treatment downregulated the anti-apoptotic Bcl2 gene while upregulating pro-apoptotic Bax and p53 genes, indicating its ability to induce programmed cell death in cancer cells. Our results demonstrate that A. pullulans AKW-derived melanin exhibits cytotoxic effects against A431, HEPG2, and MCF7 cell lines. Interestingly, the present fungal strain synthesized melanin in a simple medium without requiring precursors. The selective activity of the current melanin towards cancer cells, its ability to induce apoptosis, and its relatively low toxicity towards normal cells warrant further investigation for its development as a novel therapeutic option.