Colorectal cancer remains a major global health challenge, underscoring the need for new therapeutic agents targeting cancer metabolism. In this study, a novel series of benzamide-derived hydrazone derivatives (3a-i) was designed and synthesized as the potential Aldolase A (ALDOA) inhibitors. Their antiproliferative activity was first evaluated against HT-29 human colorectal cancer cells and L929 mouse fibroblast cells. Among the series, compounds 3a (5-bromo-2-methoxyphenyl) and 3d (5-nitrofuran-2-yl) displayed particularly potent and selective cytotoxicity, with IC50 values of 0.382 +/- 0.115 mu M and 0.101 +/- 0.066 mu M, respectively. Both compounds also effectively inhibited ALDOA (72.06 +/- 4.12% and 82.09 +/- 7.14%, respectively, at 10 mu M), reduced lactate production, downregulated hypoxia-inducible factor-1 alpha (HIF-1 alpha), and induced apoptosis, demonstrating a strong metabolic inhibition profile. Furthermore, 300 ns molecular dynamics simulations of the compound 3d-ALDOA complex revealed a stable and specific binding mode with the persistent intermolecular interactions, supporting its experimentally observed inhibitory potential. Collectively, these findings introduce a new hydrazone-based scaffold with enhanced potency and selectivity, representing a promising lead for further development in colorectal cancer therapy.

The alarming increase in antimicrobial resistance and the persistence of diseases such as tuberculosis have created an urgent demand for novel agents with broad-spectrum antimicrobial potential. In this study, eleven new hybrid molecules (1–11) bearing sulfamethizole and benzamide scaffolds were synthesized using a molecular hybridization strategy. Structural elucidation was carried out via IR, ¹H-NMR, ¹³C-NMR, mass spectrometry, and elemental analysis. The synthesized compounds were evaluated for their biological activity against a diverse panel of microorganisms, including Gram-positive and Gram-negative bacteria, dermatophyte group mold-type fungi, yeast strains, and Mycobacterium species. Biological screening results revealed that several of the compounds exhibited notable antimicrobial activity, with certain derivatives showing enhanced efficacy against mycobacterial and fungal pathogens. Among them, compound 1 drew interest with its remarkable antifungal activity against Trichophyton rubrum and Microsporum gypseum (0.008 mM MIC for both), while compound 8 emerged as a potent antitubercular lead with a notable MIC of 0.031 mM against Mycobacterium intracellulare. Besides, according to the molecular docking studies performed on CYP51 enzyme, it showed the most promising binding in this group with a − 7.82 kcal/mol docking score, which is significantly better than the standard drug fluconazole (− 5.40 kcal/mol) and comparable to the co-crystallized ligand VT1 (− 9.36 kcal/mol), confirming its high binding affinity. Furthermore, 100 ns molecular dynamics simulations confirmed the structural stability of the enzyme-ligand complex through RMSD analysis, indicating a persistent binding mode. Complementary ADME predictions revealed that the compounds possess favorable pharmacokinetic properties and follow Lipinski’s Rule of Five. These findings highlight the potential of sulfamethizole-based benzamides as promising candidates for antimicrobial drug development through a successful correlation between in vitro and in silico data.

In this study, a new 1,3,4-oxadiazole derivative, N-benzyl-5-[2-(3-trifluoromethylphenyl) amino]phenyl-1,3,4-oxadiazol-2-amine, was synthesized and comprehensively characterized using experimental and theoretical methods. The compound was obtained in 79% yield, and its structure was investigated by FT-IR, 1H NMR, 13C NMR, LC-MS, HSQC and single-crystal X-ray diffraction techniques. XRD analysis revealed that the molecule crystallizes in the monoclinic P21/c space group, and the structural parameters showed strong agreement with the DFT-optimized geometries (B3LYP/6-31G(d,p) and cc-pVDZ). Hirshfeld surface analysis indicated that H center dot center dot H, C center dot center dot H and H center dot center dot F contacts dominate the crystal packing. Frontier molecular orbital (FMO) calculations demonstrated a HOMO-LUMO energy gap of approximately 4.1 eV, suggesting moderate chemical reactivity and stability. MEP, NCI-RDG, ELF and LOL analyses further clarified the electronic distribution and non-covalent interactions supporting structural stability. Nonlinear optical (NLO) calculations revealed that the compound possesses a first-order hyperpolarizability higher than urea and greater than KDP, indicating promising NLO potential. Molecular docking studies against human butyrylcholinesterase (PDB: 4BDS) showed a binding affinity of-7.8 kcal/mol with multiple stabilizing interactions, suggesting potential anti-Alzheimer's activity. Overall, the combined experimental and computational findings highlight the compound as a promising candidate for future optical and biological applications.

Despite significant advances in cancer therapy, the discovery of new anticancer agents with improved efficacy remains an important challenge. Human DNA topoisomerases I and II are well-established therapeutic targets because of their essential roles in DNA replication and transcription. Accordingly, a series of novel etofenamate-based thiosemicarbazide, 1,3-thiazole, and 1,3,4-oxadiazole derivatives were designed and synthesized, including a new synthetic approach for the preparation of the oxadiazole derivatives, and evaluated as potential topoisomerase-targeting anticancer agents. All synthesized compounds were structurally characterized and evaluated for antiproliferative activity against the A549 human lung cancer cell line and for their inhibitory effects on human DNA topoisomerases I and II. Based on their overall biological performance, compounds 3h, 5 h, and 5i were selected for further biological characterization, including thioredoxin reductase 1 (TrxR1) inhibition, total oxidative status (TOS), Bax/Bcl-2 protein expression, Annexin V analysis, and crystal violet staining. Molecular docking studies were performed to investigate the binding modes of the lead compounds toward topoisomerases I and II. Biological evaluation identified compounds 3 h, 5h, and 5i as the most promising derivatives. Enzymatic assays revealed distinct topoisomerase inhibition profiles, with compound 5h acting as a selective topoisomerase I inhibitor and compound 5i exhibiting dual inhibitory activity against topoisomerases I and II. Molecular docking analyses supported these findings by revealing target-specific binding modes consistent with the observed inhibition profiles. Complementary cellular studies demonstrated TrxR1 inhibition, increased oxidative stress, apoptosis-associated cellular responses, and morphological alterations, providing additional mechanistic characterization of the lead compounds. Collectively, these findings establish topoisomerases I and II as relevant molecular targets for the synthesized series while broadening the biological characterization of the lead compounds through complementary cellular investigations. Compound 5i emerged as the most promising dual topoisomerase I/II inhibitor and represents a valuable lead for the further development of novel topoisomerase-targeting anticancer agents.

Despite the efforts to treat cancer with chemotherapeutic agents targeting different mechanisms, cancer is still one of the most important health problems today. The increase in cancer incidence has led researchers to discover new, effective, and selective molecules. For this purpose, novel thiosemicarbazide (3a-3i) and 1,3,4-thiadiazole derivatives (4a-4i) were synthesized from clopidogrel bisulfate and their cytotoxic activities were investigated against glioblastoma (U87) cell line and healthy fibroblast (L929) cell line by MTT assay. Among the synthesized compounds; 3b, 3g, 4b, 4d, and 4i exhibited higher cytotoxic activities than the standard drug paclitaxel against U87 cancer cells. Cell apoptosis was detected by Bax, Bcl-2, caspase-3 activity, and Annexin V assay. The results displayed that compounds 3b, 3g, 4b, 4d, and 4i induced apoptosis in U87 cells. Moreover, all compounds were investigated for DNA methyltransferase (DNMT) activity in U87 cells. DNMT enzyme activity was decreased in these compounds' treated cells. Cyclohexyl ring-bearing compound 4d, which showed the highest activity against U87 cells, was the most potent inhibitor of DNMT with an IC50 value of 5.78 +/- 1.07 mu M compared to paclitaxel (82.05 +/- 4.67 mu M). Molecular docking studies were also performed to identify the interactions between the compounds and the active sites of DNMT.

Lenalidomide (L0) is an immunomodulatory agent with a range of effects, including anticancer and antiinflammatory activity, and is commonly utilized in treating multiple myeloma. A derivative of lenalidomide (L1) has been synthesized to enhance its effects and to target different cancer cell types. In this study, the lenalidomide derivative L1, with the chemical structure 1-[2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl]-3(p-tolyl)urea, was loaded onto a novel drug delivery system (DDS), and its activity was assessed towards triple-negative breast cancer cell lines (TNBC). MIL-100, a subclass of metal-organic framework (MOF) structures, was synthesized via a microwave-assisted hydrothermal method. MIL-100 was modified with quercetin (QC) as a linker, and its drug loading capacity was optimized, achieving a 95.18 % encapsulation efficiency. Additionally, the antioxidant properties of QC contributed to enhancing the performance of the DDS. In vitro drug release studies of the final product, MIL-100@QC@L1, were successfully conducted. The cytotoxic influences of the formulation on MDA-MB-231 cells were assessed using the WST-1 assay. After treatment with 10 mu g/mL of MIL100@QC@L1 for 24 h, the cell viability decreased significantly to 47.8 %, showing superior results compared to treatments with L0 and L1 alone.

Objective: In this study it was aimed to synthesize novel 1,3,4-thiadizole bearing 4(3H)-quinazolinone compounds, elucidate their structure and evaluate their anti-biofilm activity. Methods: Four novel 4(3H)-quinazolinone compounds (1-4) were synthesized with a two step reaction starting from 5-bromoanthranilic acid. Their anti-biofilm activity was investigated. Results: The final compounds’ structures were clarified by elemental analysis and spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS). In the result of anti-biofilm activity studies, they possessed 26.0-30.0% biofilm formation inhibition. Conclusion: Among the tested compounds, 6-bromo-3-{4-[5-(4-nitrophenylamino)-1,3,4-thiadiazol-2-yl]phenyl}-2-methylquinazolin-4(3H)-one formulated compound 3 was found as the most active one with 30.0% biofilm formation inhibition.

New, selective and effective anticancer agents are urgently needed in drug research and development studies. For this purpose, some new 2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives based on clopidogrel were synthesized and characterized using spectral techniques, including IR, 1H NMR, 13C NMR and MS. The anticancer activities of the synthesized compounds were evaluated in vitro against human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC). Among these compounds, the ethyl chain-bearing compound 3 and the 4-methoxyphenyl-bearing compound 8 exhibited the most selective anticancer activities against PC3 with IC50 values of 6.81+2.14 mu M and 4.68+1.76 mu M, respectively. Apoptotic cells were investigated with AO/EB staining. Total DNMT enzyme activity and protein expression levels (DNMT1, DNMT3a, and DNMT3b) were also analyzed in compound 3 and compound 8 treated cells. Compounds 3 and 8 showed DNA methyltransferase inhibitory activity of 63.02+1.40% and 54.08+6.35%, respectively. Molecular docking studies were performed to elucidate the interaction of compounds 3 and 8 with the DNMT1 enzyme. As a result, 3 and 8 were reported to be candidates compounds for the development of DNA methyltransferase inhibitors with potent anticancer activity.

A hydrazide-hydrazone derivative, (E)-N'-(2-hydroxybenzylidene)-2-((3-(trifluoromethyl)phenyl) amino)benzohydrazide, was synthesized and characterized using various spectroscopic techniques such as FTIR, 1H-NMR and 13C-NMR spectroscopy, and X-ray diffraction. The compound crystallized in the monoclinic space group P2/n, with lattice parameters: a = 21.0586(8) Å, b = 8.1969(3) Å, c = 21.6475(10) Å, and β = 92.886(2)°. Within a single crystal cell, two crystallographically independent asymmetric molecules are present. These molecules are chemically identical but display a non-planar geometric molecular structure. The crystal structure was stabilized by C–H⋯O and C–H⋯N hydrogen bonds, which facilitate intermolecular interactions that form a three-dimensional network. The presence of effective hydrogen bond donors and acceptors contribute to the formation of a tightly interconnected three-dimensional structure. Additionally, Hirshfeld surface analysis was conducted to examine potential hydrogen bonding and spatial arrangement of atoms. This analysis quantified hydrogen bond interaction and identified atoms likely to participate in such interactions. Alongside stabilization by strong hydrogen bonds, π⋯π interactions significantly influence the packing arrangement, with interactions among the phenyl rings observable through shape index and curvedness diagrams.

Due to the lack of an effective treatment for Alzheimer's disease, there is a need for the development of new and effective compounds. The synthesis of some new hydrazone derivatives (TA1-TA14) based on Clopidogrel bisulfate has been carried out. IR, 1H-NMR, 13C-NMR, 2D-NMR (HSQC) and MS spectroscopic techniques were used to elucidate the chemical structures of the compounds. Antioxidant and cholinesterase activities of the compounds were evaluated. Compound TA2 bearing bromo substituent has the highest antioxidant activity in the series. Compound TA11 bearing methoxy substituent exhibited the highest inhibitory activity in the series with IC50 values of 8.540±0.015 µM and 7.980±0.026 μM against AChE and BChE, respectively. Kinetic studies (Lineweaver-Burk plots) revealed that TA11 was a competitive inhibitor. In addition, molecular docking studies aimed to elucidate the interactions between these designed compounds and key enzymes, including AChE and BChE. TA11 has been evaluated as a promising candidate for further studies to develop new agents in the fight against Alzheimer's disease.

This study involved the design, synthesis and evaluation of a series of novel thiosemicarbazide and thiazolylhydrazone derivatives. The synthesized compounds were tested for cytotoxic effects SH-SY5Y neuroblastoma cells, as well as NIH-3T3 normal cell line using the MTT assay. Among the tested compounds, 3b, 3d, 3i, 4b, 4d and 4i exhibited IC50 values ranging from 1.97 mu M to 3.22 mu M in the SH-SY5Y cancer cell line with lower cytotoxicity toward NIH-3T3 cells. Moreover, all compounds were also screened for their topoisomerase I and II inhibitory activity and compound 3b completely inhibited the topoisomerase I enzyme, whereas all compounds showed potent topoisomerase II inhibitory activity. Docking studies were performed to identify the mode of binding of the tested compounds to the active site of topoisomerase I and II. In conclusion, N-(4-(2-((2-chlor- ophenyl)carbamothioyl)hydrazine-1-carbonyl)phenyl)benzamide (3b) emerges as a promising inhibitor of topoisomerase I and II and holds potential as a lead compound in the quest for novel anticancer agents.

A new Schiff base compound of N'-[(2,6-dichlorophenyl)methylidene]-2-{[3-(trifluoromethyl)phenyl]amino}benzohydrazide was synthesized and characterized through various spectroscopic techniques, including infrared, 1H NMR, 13C NMR spectroscopy and X–ray diffraction. Experimental results collected by XRD were compared with theoretical results obtained from Density functional theory method. Hirshfeld surface analysis was used to obtain three dimension molecular surface and two dimension fingerprint plots to illustrate the intermolecular bonding. Theoretical calculations provide valuable insights into both global and local chemical activity, as well as the properties of molecules and chemicals, including their nucleophilic and electrophilic nature. The DFT method at B3LYP/6–311++G (d,p) basis set was employed to study the optimized structure and geometric parameters, as well as to explore the frontier molecular orbitals, global reactive parameters, Mullikan population analaysis, Natural bond orbital and molecular electrostatic potential characteristics which cannot be obtained by experimental methods. Additionally, electrophilicity based charge transfer study was carried out with DNA bases to determine the direction of charge transfer. Finally, an investigation was carried out using molecular docking analysis to examine the binding energies of the title compound with PDB ID: 2QDJ protein target. The analysis yielded significant insights into the possible interactions, offering valuable findings in the process.

Designing new compounds from existing chemotherapeutic drugs to enhance inhibitory effects on tumor cells while overcoming multidrug resistance is one of the important strategies for new drug discovery in medicinal chemistry. A new series of urea and thiourea derivatives based on Lenalidomide as potential anticancer agents have been designed and synthesized. In vitro anticancer activity assay against Caki cancer cells and HUVEC endothelial cells revealed that 1-(4-methylphenyl)-3-[2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl]urea (11) exhibited the highest anticancer activity and selectivity in the series with IC50 values of 9.88 and 179.03 mu M, respectively. Among the compounds, 11 showed significant HDAC1 inhibiton of 68.02 +/- 2.44% at 10 mu M concentration. TGF-beta, Bax, Bcl-2 protein levels and scratch assay were analyzed in Caki cells. As a result, compound 11 induced apoptosis in Caki cells. In this study, it has been demonstrated that compound 11 can be a lead compound for further detailed investigation in renal cancer treatment. Through molecular docking studies, it was determined that the most active compound, 11, forms stable interactions with key residues in the enzyme's active site, particularly engaging in hydrogen bonds with GLY149 and coordinating with the zinc ion in the HDAC1 active site. These interactions are crucial for the observed inhibitory activity. Molecular dynamics simulation revealed the binding event of the most active compound with class I histone deacetylase and the stability of the complex in a biological environment.

Hydrazide-hydrazone derivatives have garnered significant interest from researchers globally due to their wide range of biological activities, including antiviral, anticancer, and anti-inflammatory properties. In this study, a novel series of etofenamate hydrazide-hydrazone compounds (2a-2s) and their Cu(II) complexes (3a-3s) were designed and synthesized. The compounds were characterized using various analytical techniques such as FT-IR, 1H NMR, 13C NMR, MS, and elemental analysis. Additionally, the compound 2c and Cu(II) hydrazone complex 3a were further characterized using single X-ray crystallography. The anti-proliferative activity of the compounds was evaluated against Ishikawa human endometrial cancer cell line and non-tumour L929 cells using MTT assay. Additionally, the apoptotic potential of the compounds was investigated through caspase-3 activity, Bax and Bcl-2 gene expression analysis, and annexin-V binding. Furthermore, carbonic anhydrase IX activity and in silico studies were conducted to elucidate the mechanism of action. Overall, compound 3s demonstrated significant antiproliferative effects with an IC50 value of 0.27±0.01 µM against Ishikawa cells.

In this study, synthesis of some new hydrazone derivatives based on articaine was carried out. MDA-MB231 (triple negative human breast cancer cells) and HUVEC (human umbilical vein endothelial cells) cells were used to investigate the cytotoxic activity of hydrazone compounds. Induction of apoptosis and cell viability were assessed by AnnexinV-PI binding levels and Bax-Bcl2 gene expression levels. Inhibitory activities of the compounds against carbonic anhydrase enzyme were also evaluated. Compounds 2b and 2m exhibited the highest cytotoxic activity against MDAMB-231 cells with IC50 values of 16.62 +/- 1.18 mu M and 18.56 +/- 2.36 mu M, respectively. Similarly, the CA inhibition of 2b and 2m was also determined to be the highest in the series.

Thiosemicarbazide and also 1,3,4-thiadiazole derivatives have been garnering substantial attention from researchers worldwide due to their expansive range of biological activities, encompassing antimicrobial, anti-inflammatory, and anticancer properties. Herein, we embarked on a comprehensive investigation in this study, introducing a novel series of thiosemicarbazides ( 3a–3i ) and their corresponding 1,3,4-thiadiazole ( 4a–4i ) derivatives. The compounds were meticulously designed, synthesized, and subjected to meticulous characterization using various spectroscopic methods such as FT-IR, 1 H-NMR, 13 C-NMR, and elemental analysis. Afterward, their potential anti-proliferative effectiveness was assessed using MTT assay against two cancer cell lines (U87 and HeLa) and normal fibroblast cells (L929). Among the compounds, 4d showed the highest cytotoxic activity against U87 and 4i against HeLa. Compound 3b exhibited selective cytotoxic activity against both cancer cells. Among the molecules with selective activity against the U87 cell line; 3a , 3b , 4d and 4e were further evaluated by caspase-3 activity levels, Bax and Bcl-2 protein expression, and total oxidant status assay. Besides, carbonic anhydrase IX activity studies were also performed in order to understand the underlying mechanism of action. The results indicated that compound 4e showed higher efficacy than standard acetazolamide (IC 50 = 0.58 ± 0.02 µM) with an IC 50 value of 0.03 ± 0.01 µM. Furthermore, molecular docking studies were carried out using carbonic anhydrase IX crystals to determine the compound’s interactions with the enzyme’s active sites. This comprehensive investigation sheds light on the intricate interplay between molecular structure and biological activity, providing valuable insights into the therapeutic potential of these compounds.

The freshwater blenny Salaria fluviatilis (Asso y del Rio, 1801) is a freshwater species that favors demersal environments. Individuals of this species live in rivers and brooks of Europe, North Africa and Israel. Three specimens of S. fluviatilis (TL 80.82 mm, 60.98 mm and 64.14 mm) collected from Kızılırmak River – Kesikköprü Bridge, Turkey during July 2021 showed deformities in both pectoral and pelvic fins. Degeneration was noted in the pectoral fin rays particularly the last ventral two soft rays (soft ray no. 13 and 14 counting from dorsal to ventral). They also look smaller than those in the normal specimen do. The degeneration in the soft ray no. 13 is less severe than soft ray no. 14. The x-ray of the abnormal specimen showed no other pectoral fin rays were deformed and the pectoral girdle was normal. In both specimens of S. fluviatilis that showed pelvic fin rays degeneration, the whole left pelvic fin and the right pelvic fin were completely degenerated and no soft rays are present. The possible causative factors of these anomalies are discussed. Our finding highlights the need for closer monitoring of the freshwater environment and for the identification of the specific factor that caused these abnormalities.

In this study, a series of hydrazide-hydrazone derivatives (3a-3u) were synthesized and evaluated for their anticancer activities against prostate cancer cell line (PC-3), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and human umbilical vein endothelial cells (HUVEC) using MTT assay. In particular, compound 3h having a pyrrole ring was found to be the most potent derivative with IC50 = 1.32, 2.99, 1.71 µM against PC-3, MCF-7, HT-29 cancer cell lines respectively using paclitaxel as a standard compound. Furthermore, compound 3h was subjected to further biological studies such as caspase-3 activity and Annexin-V assay to evaluate their inhibitory potentials. The activity results displayed that compound 3h increased caspase-3 activation and the number of cells to early apoptosis. The additional studies like pharmacokinetics, bioavailability scores and drug-likeness properties were also evaluated. The in silico pharmacokinetics predictions displayed that the bioavailability of these compounds may be high.

The aim of this study is to perform therapeutic drug monitoring for isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) in pediatric tuberculosis patients. The study was carried out in 3 different training-research hospitals in Istanbul, Turkiye between 2011 and 2012. The pediatric patients (aged <= 14 years) who initiated the standard primary anti-tuberculosis therapy were included in this study. The serum samples were collected 3 hours after the first medication doses were given on the 5th day of treatment. Chromatographic experiments were performed on an Agilent 1100 High-Performance Liquid Chromatography (HPLC) system, and the separation was carried out on a Nova-Pak C-18 (3.9x150 mm, 5 mu m, Merck) analytical column. In this HPLC method, the gradient elusion delivered 3% to 40% (v/v) acetonitrile in phosphate buffer was used, and diode array detector. Twenty-three children (60.9% male) patients were included with a mean age of 111.70 +/- 59.94 months. Plasma levels were measured sub-therapeutically for INH in 14, RIF in 10, and PZA in 5 patients, according to the normal range of adult patients. Maximum plasma concentrations after three hours were found between 0.53-14.02 mg/L for INH, 11.17-60.39 mg/L for PZA, 2.15-16.75 mg/ L for RIF. In conclusion, this method has been successfully applied to simultaneously determine RIF, INH, and PZA plasma levels in pediatric tuberculosis patients. RIF and INH plasma levels were found to be lower in pediatric patients with tuberculosis compared to target range of adult patients.

In this study, a series of 1,3,4-thiadiazole (1b-9b) and 1,2,4-triazole-3-thione (1c-9c) derivatives were synthesized. The reaction proses was carried out with the cyclocondensation of suitable 1,4-disubstituted thiosemicarbazide derivatives (1a-9a). The structures of the synthesized compounds were confirmed by the data obtained from elemental analysis, HPLC, UV, IR, H-1-NMR and MS spectra. All of the compounds were tested for their cytotoxic activities against L929 fibroblast cells by MTT method. It was determined that the tested compounds 1a-9a, 1b-9b and 1c-9c were not cytotoxic at the studied concentrations (5.0 mu g/mL and 10.0 mu g/mL) in L929 cell lines. Compounds 1a-c, 2a-c, 3a-c, 4a-c, 5a-c and 8a-c showed increased growth inhibition whereas compounds 6a-c, 7a-c and 9a-c showed decreased growth inhibition on L929 cell lines