A549 Cell Lines Research Articles

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.

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.

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.

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.

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.

Chronic stress promotes non-small cell lung cancer (NSCLC) progression through circMBOAT2 upregulation mediated by CTCF.

Circular RNA (circRNA) has been demonstrated to play a pivotal role in tumor development. This study aimed to investigate the regulatory mechanism of circMBOAT2 in non-small cell lung cancer (NSCLC) and its association with tumor growth induced by chronic stress. We constructed stably transfected A549 and H1299 cell lines with circMBOAT2 overexpression and knockdown. Colony formation, scratch healing, Transwell and CCK-8 assays were conducted to evaluate the effects of circMBOAT2 in the presence or absence of norepinephrine (NE) treatment on the proliferation, migration, and invasion of NSCLC cells, respectively. Additionally, A chronic unpredictable mild stress (CUMS)-induced depression with heterotopic transplantation LLC and injection of antisense oligonucleotides (ASOs) targeting circMBOAT2 mouse model was established to evaluate the effect of chronic stress on tumorigenesis via circMBOAT2. Moreover, we investigated the regulatory effect of CCCTC binding factor (CTCF) on circMBOAT2 expression through in vivo and in vitro silencing of CTCF. Our results revealed a significant upregulation of circMBOAT2 in NSCLC cell lines and tumor tissues. circMBOAT2 knockdown inhibited the proliferation, migration, and invasion of NSCLC cells, while NE treatment reversed the cell suppression effect caused by circMBOAT2 knockdown. Notably, CUMS promoted tumor growth, while silencing circMBOAT2 inhibited tumor growth in vivo. Furthermore, we identified CTCF as the upstream regulator of circMBOAT2, which exhibited upregulation in NSCLC cells and tissues. Knockdown of CTCF reversed the promotional effect of CUMS on circMBOAT2 expression and tumor growth. Our findings provide evidence that CTCF mediates chronic stress in promoting of NSCLC progression through circMBOAT2. circMBOAT2 may serve as a potential biomarker and therapeutic target for NSCLC as well as the treatment of comorbid depression in NSCLC patients.

Synthesis of New Chromen-5-one Derivatives from Dimedone and their Antiproliferative Evaluations against Selected Cancer Cell Lines Together with Hepatocellular Carcinoma and Cervical Carcinoma

<p>Background: The coumarin nuclei, which exist in many heterocyclic compounds, has gained a lot of attention over the past decade due to their wide range of biological activities such as antibacterial, anticoagulant, antiviral, antifungal, anticancer, and anti-inflammatory properties. </p> <p> Objective: The multi-component reactions of 5,5-dimethylcyclohexane-1,3-dione with acetophenone derivatives and triethoxymethane produced biologically active target chromene molecules and their fused derivatives. </p> <p> Methods: The reaction of 5,5-dimethylcyclohexane-1,3-dione and each of triethoxymethane and acetophenone derivatives 3a-g in absolute ethanol containing triethylamine gave the 4,6,7,8-tetrahydro-5H-chromen-5-one derivatives 4a-g. Compounds 4a-d were used for further heterocyclization reactions to produce biologically active fused pyrazole, thiophene, and thiazole derivative corporate with the chromenes caffold. </p> <p> Results: The cytotoxicity of the synthesized compounds were evaluated using six cancer cell lines together with c-Met kinase and PC-3 cell line inhibitions. In addition, cytotoxicity toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa was carried out as well as the in-vitro cytotoxic potential for all compounds against peripheral blood lymphocytes (PBL) extracted from healthy donors. Morphological changes of the A549 cell line by the two most active compounds were also studied. </p> <p> Conclusion: The synthesized heterocyclic compounds were originally obtained from 5,5-dimethylcyclohexane1,3-dione. Several of the produced compounds exhibited high inhibitions toward several cancer cell lines proving high inhibitions, therefore, encouraging further studies to synthesize heterocyclic compounds based on chromene scaffold.</p>

Synthesis, antimicrobial, anticancer activity, 3D QSAR, ADMET properties, and in silico target fishing of novel N,N-disubstituted chloroacetamides

The recent FDA approval of afatanib, ibrutinib, and osimertinib, which covalently bind to specific cysteine residues in target kinases, has renewed interest in covalent drug discovery. Besides α,β-unsaturated carbonyls, chloroacetamides have emerged as popular warheads for designing targeted covalent inhibitors. In this study, we synthesized thirteen N,N-disubstituted chloroacetamides (1–13) by acylating secondary amines with chloroacetyl chloride, selecting substituents to provide a wide range of lipophilicity. We evaluated their anticancer and antimicrobial activity, finding five compounds with significant cytotoxicity against HeLa, K562, and A549 cell lines (IC50 <10 μM). Notably, compound 10 activated caspases 3, 8, and 9, promoting both intrinsic and extrinsic apoptotic pathways, while compounds 9–12 were strong apoptosis inducers. A 3D QSAR model showed that aromatic substituents on nitrogen atoms reduced HeLa potency, whereas the overall molecular shape had a positive effect. ChemBL and pharmacophoric similarity searches suggested potential anticancer targets, including alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), glycogen synthase kinase-3β, and calmodulin. Docking studies indicated that chloroacetamides bind to ADH and ALDH via hydrogen bonds and hydrophobic interactions. Pharmacokinetics predictions suggest that chloroacetamides are druglike molecules with promising ADMET properties.

Synthesis, Characterization, and In vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors

Introduction: Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem. Method: The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe2+ cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized. Result: The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC50=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC50 = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC50=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both in vitro and in silico methods revealed a compound with high aromatase inhibitor potential. Conclusion: The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Synthesis and evaluation of in vitro antioxidant, anticancer, and antibacterial properties of new benzylideneiminophenylthiazole analogues

A series of new benzylideneiminophenylthiazole analogues were designed and synthesized. Common spectroscopic methods, such as FT-IR, 1H-, 13C-NMR, and MASS spectra, and elemental analysis, were used to confirm the molecular structures. Then, the antioxidant, cytotoxicity, and anti-bacterial effects of synthesized analogues were assessed against 2,2-diphenyl-1-picrylhydrazyl (DPPH), three cancer cell lines, and two bacterial strains, respectively. Among the analogues, 7f was detected as the most potent compound for antioxidant activity. Moreover, the compounds 7b, 7f, and 7 g exhibited the maximum cytotoxicity activity against MCF-7, HepG-2, and A549 cell lines, respectively. Finally, 7e showed the highest anti-bacterial activity against both S. aureus and E. coli strains. It was concluded from the antioxidant, cytotoxicity, and anti-bacterial effects that the benzylideneiminophenylthiazoles might serve as candidate molecules for the development of small molecules with medicinal potential.

Spectral studies of a selenium(IV) vitamin B3 compounds prepared in the form of nanometer using simple chemical reactions to further use as antioxidant in the preparation of drugs

The current study dealt with selenium metal ion complexes with mixed ligands, consisting of nicotinamide (vitamin B3) as the first ligand, and amino acids such as (histidine, tryptophan, and tyrosine) as the second ligand. It was synthesized in (1:1:1) (selenium: vitamin: amino acid) in molar ratio. By using different characterization techniques such as elemental analysis, the conductance, FTIR, XRD, UV-Vis, TG/DTG, 1H-NMR, XRD, SEM, TEM analyses, the chemical structures and the morphological properties of the synthesized complexes were checked and discussed. The nicotinamide was coordinated as monodentate ligand via the nitrogen of pyridine ring but all amino acids as a secondary ligand coordinated as bidentate through oxygen of carboxylic group and nitrogen of amino group. The complexes demonstrate antioxidant activity with potent scavenging property, the synthesized in the form of nanometer give great importance in increasing efficiency of absorption of human cells to selenium giving the highest efficiency of medical product. All complexes in this study were evaluated for their anticancer effect towards HepG2 and A2780 cell lines. From these data the complex (Se/Nia/ Tyr) can be used as antitumor agents. KEY WORDS: Selenium, Amino acids, Vitamin B3, Mixed ligand, Complexes, Antioxidant Bull. Chem. Soc. Ethiop. 2024, 38(6), 1759-1774. DOI: https://dx.doi.org/10.4314/bcse.v38i6.20

LUCAT1 Activates the Malignant Phenotypes of Lung Cancer Cells via Regulating P53 Ubiquitination.

Long non-coding RN (lncRNAs) have been implicated in lung cancer, but the mechanisms stay unclear. We investigated the theatrical role and mechanism of lncRNA Lung cancer associated transcript 1 LUCAT1 in the malignant progress of lung cancer. From May 2022 to March 2023, a total of thirty normal and cancerous tissues were collected from patients diagnosed with non-small cell lung cancer at Zhongke Gengjiu Hospital in Anhui Province, China. The human SPC-A1 and A549 cell lines were chosen as the subjects for the relevant cellular experiments in this study. LncRNAs were expressed in a different manner identified by bioinformatics methods, and the expression levels in lung cancer tissues as well as cells were verified by the qRT-PCR assay. The biological role of LUCAT1 in NSCLC was determined by CCK-8, EdU, and transwell assay. The regulation of ubiquitin of P53 by LUCAT1 was studied, which showed that LUCAT1 was significantly elevated in NSCLC cell lines and patients' tissues (P<0.05). High levels of LUCAT1 promoted the proliferation, invasion, and migration of NSCLC cells. Mechanism studies showed that LUCAT1 was mainly located in the nucleus, which bound to P53 and mediated the ubiquitinated degradation of P53. Meanwhile, LUCAT1 knockdown attenuated the ubiquitination process of P53. In addition, rescue experiments illustrated that LUCAT1 induced the proliferation and invasion of NSCLC cells, and played a key role in the survival and tumorigenicity of NSCLC cells by mediating the ubiquitination of P53. Collectively, LUCAT1 activated the malignant phenotypes of NSCLC cells via regulating P53 ubiquitination, which provided a new idea for the diagnosis and treatment of NSCLC.