Cell Line HepG2 Research Articles

Exploiting the bile acid binding protein as transporter of a Cholic Acid/Mirin bioconjugate for potential applications in liver cancer therapy.

Bioconjugation is one of the most promising strategies to improve drug delivery, especially in cancer therapy. Biomolecules such as bile acids (BAs) have been intensively explored as carriers, due to their peculiar physicochemical properties and biocompatibility. BAs trafficking is regulated by intracellular lipid-binding proteins and their transport in the liver can be studied using chicken liver Bile Acid-Binding Proteins (cL-BABPs) as a reference model. Therefore, we conceived the idea of developing a BA-conjugate with Mirin, an exonuclease inhibitor of Mre11 endowed with different anticancer activities, to direct its transport to the liver. Following computational analysis of various BAs in complex with cL-BABP, we identified cholic acid (CA) as the most promising candidate as carrier, leading to the synthesis of a novel bioconjugate named CA-M11. As predicted by computational data and confirmed by X-ray crystallographic studies, CA-M11 was able to accommodate into the binding pocket of BABP. Hence, it can enter BAs trafficking in the hepatic compartment and here release Mirin. The effect of CA-M11, evaluated in combination with varying concentrations of Doxorubicin on HepG2 cell line, demonstrated a significant increase in cell mortality compared to the use of the cytotoxic drug or Mirin alone, thus highlighting chemo-sensitizing properties. The promising results regarding plasma stability for CA-M11 validate its potential as a valuable agent or adjuvant for hepatic cancer therapy.

Orange peel-mediated synthesis of silver nanoparticles with antioxidant and antitumor activities

Orange (Citrus sinensis L.) is a common fruit crop widely distributed worldwide with the peel of its fruits representing about 50% of fruit mass. In the current study, orange peel was employed to mediate the synthesis of silver nanoparticles (AgNPs) in a low-cost green approach. Aqueous extracts of suitably-processed peel were prepared using different extraction methods; and their phytochemical profile was identified. Based on phytochemical screening, amount of main phytochemicals, free radical-scavenging ability, reducing power and antioxidant activity, the peel extract prepared by boiling seemed to be the most promising. Thus, major compounds of this extract were identified by gas chromatography-mass spectrometry. Potency of the peel extract to mediate the synthesis of AgNPs was then monitored by visual observation, UV-visible spectroscopy, energy dispersive X-ray analysis, transmission electron microscopy and zetametry. Color change of the reaction mixture to brown and absorption peak at 450 nm indicated AgNPs formation. Characterization of AgNPs revealed spherical shape, size of 30–40 nm, zeta potential of -18.2 mV and yield conversion of 82%. The as-synthesized AgNPs had antioxidant capacity (free radical-scavenging ability, reducing power and antioxidant activity) lower than that of the orange peel extract. However, these biogenic AgNPs had antitumor activity (IC50 of 16 ppm against HCT-116 and 1.6 ppm against HepG2 cell lines) much higher than the peel extract that was completely non-toxic to the considered cell lines.

Repercussion of manufacture and digestion process of foods enriched with sesame flour on the antioxidant response of human hepatocyte cultures

As natural bioactive compounds with recognized antioxidant power, polyphenols may impact on several diseases associated with oxidative stress. In this study, defatted sesame flour (DSF) was investigated as a potential source of dietary polyphenols and a functional ingredient. Additionally, the impact of manufacture and digestion processes on the biological efficacy of the resulting extracts in the HepG2 cell line was explored. For this purpose, polyphenolic extracts were obtained from three sources: DSF, a control sweet cookie formulation and 10% DSF-enriched cookies. In addition, extracts of potentially bioaccessible polyphenols from in vitro digested cookies were collected. Cells were incubated with all these extracts and then injured with H2O2. Intracellular oxidative state and viability, antioxidant enzymes activities, glutathione (GSH) content, and oxidation of proteins and lipids were analyzed. The results showed DSF pro-oxidant actions on the cellular redox state, which hormetically enhanced the antioxidant response. Similarly, biological activity of DSF enriched cookies was found to persist after manufacture and digestion, promoting lipid peroxidation alleviation and GSH replenishment.By promoting an antioxidant response in cells, DSF may be considered for functional incorporation, offering preventive benefits and protective action to counterbalance oxidative damage. This study contributes to highlighting the benefits of DFS validating its final biological effects in a cellular model.

Effective Synthesis of C20-epi-Isothiocyanato-Salinomycin and Its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, Hela, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

Global and Targeted Metabolomics for Revealing Metabolomic Alteration in Niemann-Pick Disease Type C Model Cells.

Niemann-Pick disease type C (NPC) is an inherited disorder characterized by a functional deficiency of cholesterol transport proteins. However, the molecular mechanisms and pathophysiology of the disease remain unknown. In this study, we identified several metabolite characteristics of NPC that may fluctuate in a cellular model of the disease, using both global and targeted metabolomic analyses by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Three cell lines, HepG2 cells (wild-type[WT]) and two NPC model HepG2 cell lines in which NPC1 was genetically ablated (knockout [KO]1 and KO2), were used for metabolomic analysis. Data were subjected to enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The enrichment analysis of global metabolomics revealed that 8 pathways in KO1 and 16 pathways in KO2 cells were notably altered. In targeted metabolomics for 15 metabolites, 4 metabolites in KO1 and 10 metabolites in KO2 exhibited statistically significant quantitative changes in KO1 or KO2 relative to WT. Most of the altered metabolites were related to creatinine synthesis and cysteine metabolism pathways. In the future, our objective will be to elucidate the relationship between these metabolic alterations and pathophysiology.

Ultrasonic synthesis, characterization, DFT and molecular docking of a biocompatible Zn-based MOF as a potential antimicrobial, anti-inflammatory and antitumor agent

Zinc metal–organic frameworks have emerged as promising candidates, demonstrating excellent biological properties stemming from the unique characteristics of MOFs and zinc. In this study, we employed a facile method to synthesize a zinc metal–organic framework [Zn(IP)(H2O)] using ultrasound irradiation, with the linker being isophthalic acid (IPA) (1,3-benzene dicarboxylic acid). The parent Zn-MOF and two Ag/Zn-MOF samples prepared via loading and encapsulation methods were comprehensively characterized using various techniques, including FT-IR, XRD, SEM, TEM, N2 adsorption–desorption isotherm, UV–vis spectroscopy and TGA. The parent Zn-MOF and two Ag/Zn-MOF samples exhibited a broad spectrum of antibacterial effects. Remarkably, genomic DNA of P. aeruginosa was effectively degraded by Zn-MOF, further supporting its potent antibacterial results. The free radical inhibition assay demonstrated a 71.0% inhibition under the influence of Zn-MOF. In vitro cytotoxicity activity of Zn-MOF against HepG-2 and Caco-2 cell lines revealed differential cytotoxic effects, with higher cytotoxicity against Caco-2 as explored from the IC50 values. This cytotoxicity was supported by the high binding affinity of Zn-MOF to CT-DNA. Importantly, the non-toxic property of Zn-MOF was confirmed through its lack of cytotoxic effects against normal lung cell (Wi-38). The anti-inflammatory treatment of Zn-MOF achieved 75.0% efficiency relative to the standard Ibuprofen drug. DFT and docking provided insights into the geometric stability of Zn-MOF and its interaction with active amino acids within selected proteins associated with the investigated diseases. Finally, the synthesized Zn-MOF shows promise for applications in cancer treatment, chemoprevention, and particularly antibacterial purposes.

Anti-proliferative 2,3-dihydro-1,3,4-thiadiazoles targeting VEGFR-2: Design, synthesis, in vitro, and in silico studies

In this study, we present the design, synthesis, and evaluation of six new thiadiazole derivatives designed as VEGFR-2 inhibitors. The most promising compound, 18b, demonstrated promising inhibitory activity against VEGFR-2, with an IC50 value of 0.165 µg/mL. The in vitro assessments on MCF-7 and HepG2 cell lines revealed the superior anti-proliferative effects of compound 18b, exhibiting IC50 values of 0.06 and 0.17 µM, respectively. Further investigations into the cell cycle distribution of compound 18b on MCF-7 cells exhibited a cell cycle arrest at the S phase (52.96 %) and significantly reducing the percentage of cells in the G0-G1 and G2/M phases. Additionally, compound 18b demonstrated a remarkable pro-apoptotic effect, with 45.29 % total apoptosis, characterized by both early and late apoptosis, and minimal necrosis. These findings were corroborated by RT-PCR analysis, revealing a significant downregulation of the anti-apoptotic gene Bcl2 and upregulation of the pro-apoptotic gene BAX in compound 18b-treated cells compared to control MCF-7 cells. Moreover, in silico studies involving molecular docking, Density Functional Theory (DFT) calculations, Molecular Dynamics (MD) simulations, MM-GBSA, Principle Component Analysis of Trajectories (PCAT), in addition to Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions underscored the molecular interactions, energetics, and pharmacokinetic properties of compound 18b and the other derivatives further supporting its potential. Our integrated approach, combining in vitro experimens with in silico predictions provides valuable insights into the therapeutic potential of compound 18b as a robust VEGFR-2 inhibitor and lays the groundwork for future optimization.

Sulfonylhydrazide Derivatives as Potential Anti-cancer Agents: Synthesis, In Vitro and In Silico Studies.

The synthesis of new agents for cancer treatment persists due to its global lethality. A series of thirteen derivatives, namely salicylic acid-5-sulfohydrazide (SA-SH) analogs, were designed and synthesized from 5-(chlorosulfonyl)-2-hydroxybenzoic acid via nucleophilic substitution reaction with different acid hydrazides, thiocarbohydrazide & thiosemicarbazide scaffolds. Confirmation of the designed derivative's structures employed various spectroscopic techniques (FT-IR and NMR) and elemental analysis. The newly synthesized synthons were evaluated for cytotoxic activity against HepG-2 and HCT-116 cell lines in comparison to Doxorubicin. Notably, SA-SH derivatives (5, 7, 8a, 8b and 11) exhibited significantly higher efficacy against HepG-2 and HCT-116 cell lines than other analogs. Furthermore, compound (8a) demonstrated a superior activity against HepG-2 cell lines with IC50 values of 3.99 ± 0.2 μM than the reference drug, Doxorubicin, (IC50 HepG-2 = 4.50 ± 0.2 µM). The molecular docking simulation of the most active SA-SH derivatives and the reference drug doxorubicin into the active site of FGFR4 (fibroblast growth factor receptor, the predominant isoform expressed in human hepatocytes) (PDB ID: 6V9C) proved the usefulness of hybridizing salicylic scaffold with SO2 and hydrazide moieties as a promising approach in designing new anticancer agents. Finally, ADME and drug-likeness features of the most active compounds compared to positive controls were investigated to increase the success possibilities in clinical trials and they were found to be promising candidates for further investigation and development as drugs.

Abstract C112: Hemp extract attenuates the proliferation of hepatocellular carcinoma cells- derive cells from racially diverse populations by inhibiting the Interferone-1 signaling pathway

Abstract Hepatocellular Carcinoma (HCC) is a highly fatal disease where race/ethnicity plays a vital role in determining incidence, mortality, and survival rates. The incidence of HCC is highest in Asia and Africa. Furthermore, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic white patients. The HCC patients might benefit from a holistic dietary approach, including hemp extract, along with their clinical treatment. Our bioinformatics analysis of The Cancer Genome Atlas (TCGA) identified the IFN-I signaling genes (ISGs) as the most significantly enriched pathway in AA/Black HCC patients. Consistent with this finding, RNA-seq analysis of archived HCC tumors from white (n=14) and AA/Black (n=18) patients further confirmed the upregulation of ISGs in these cohorts. Due to the severe toxicity of the currently available cancer treatments, there is also a demand for the development of alternative therapies with high efficacy and low side effects. We characterized 16 varieties of hemp for their polyphenols, antioxidation, CBDs, and terpenes contents and determined the effects of hemp extracts on the proliferation of HepG2 (white patients), Hep3B, and O/20 (Black patients), and HuH-7 (Asian Patient) HCC cell lines. Among different hemp varieties, KY-Plume extract showed the highest concentration of polyphenols, antioxidation activity, CBDA, and terpenes. It also most potently inhibited the growth of all HCC cell lines (IC50s 20-25 mg/ml), irrespective of their racial origin. Hemp treatment reduced the phosphorylation of the IFN downstream mediators, Jak-1, Tyk2, STAT1, and STAT2, in all HCC cell lines. In addition, hemp treatment also inhibited phosphorylation/activation of PI3K-Akt-mTOR and MAPK pathways. Currently, research is underway to identify the active chemical agent in hemp and test it on other patient-derived HCC lines and in an in vivo model. In conclusion, our data suggest that hemp can attenuate HCC proliferation by inhibiting multiple cellular signaling pathways, including the IFN-1 pathway. Our data suggest that HCC patients might benefit from a holistic dietary approach, including hemp extract, along with their clinical treatment. (Funded: Even-Allen-USDA and P20 CA264068-01-NIH). Citation Format: Rafat A Siddiqui, Haiwen Li, Ramesh Dhakal, Milton O Faison, Devanand Sarkar.. Hemp extract attenuates the proliferation of hepatocellular carcinoma cells- derive cells from racially diverse populations by inhibiting the Interferone-1 signaling pathway [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C112.

Collagen I Increases Palmitate-Induced Lipotoxicity in HepG2 Cells via Integrin-Mediated Death.

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on the HepG2 cell line after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 cultured in the absence or presence of collagen I. HepG2 cultured in the absence or presence of collagen I was exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expression, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, and expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. However, PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than in those cultured in the absence of collagen I and was associated with increased α2β1 receptors. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I.

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.

Phytochemical Study of Stachys iva Griseb. and In Vitro Evaluation of AhR Transcriptional Activity

AbstractGenus Stachys L. consists of approximately 365 species, distributed mainly in temperate regions. Several members of this genus are widely used in the traditional medicine of different countries worldwide. In Greece, 54 Stachys taxa are found in parts of the mainland and/or insular country. The present study focused on the phytochemical investigation of Stachys iva Griseb. and the in vitro anti‐inflammatory evaluation of the isolated compounds. In total, eighteen compounds were isolated and identified from the dichloromethane‐methanol extract, belonging to iridoids, flavonoids, phenylethanoid glycosides, and phenolic acids. An in vitro approach assessed the aryl hydrocarbon receptor (AhR) modulatory effects of these compounds, revealing an AhR agonistic activity of the flavonoid aglycones apigenin and cirsimaritin in HepG2 and HT29 cell lines. The present study contributes to the evidence of the traditional uses of Stachys spp. and its bioactive constituents, justifying the ethnopharmacological use as an anti‐inflammatory plant genus.

Ultrasound-assisted Synthesis of Novel 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3, 4-thiadiazol-5-yl]-3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazoles: Anticancer Activities, Apoptotic, Cell Cycle, Molecular Docking, and ADMET Studies

Abstract: A novel series of 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3,4-thiadiazol-5-yl]-3-(2-oxo-2Hchromen- 3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazoles (2a-i) and 3 was synthesized in good yields. The methodology was depended on a one-pot four-components reaction of hydrazine hydrate, alkyl(aryl) isothiocyanate, 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (1), and acetic anhydride in acetic acid under ultrasound irradiation. The spectral tools confirmed the structures of all synthesized compounds. Using the standard SRB method, the designed compounds were screened for their in vitro cytotoxicity properties against PC3, HepG2, and HCT116 human cancer cell lines. Products 2a and 2c worked best against all cancer cells tested, as well as doxorubicin. Apoptosis and cell cycle analyses were performed for the bioactive products 2a and 2c. Both products strongly impacted all tumor cells in the late apoptotic pathway and significantly inhibited all cancer cell types under investigation in both the S and G2 phases. After that, a molecular docking study was carried out on products 2a and 2c to investigate how they interact with the CDK-8 receptor. The ADMET prediction suggested that these bioactive products may be effective anticancer treatments.

The impact of wastewater treatment plants on the composition and toxicity of pollutants in urban rivers in Nanjing, China

Widespread wastewater pollution is one of the biggest challenges threatening the ecological health of rivers. It is crucial to identify the toxic changes of effluents after entering urban rivers as well as the toxic substances in the complex chemical mixtures found in these urban rivers. This study used HepG2 cell line for cytotoxicity test to evaluate the ecological impact of effluents on urban rivers. Water samples were collected from the Xingwu River and Yunliang River in Nanjing, China. The bacterial communities in the lower reaches of urban rivers were altered due to the differences in total nitrogen and nitrate nitrogen. The complex chemical mixtures collected in the urban rivers were divided into 10 fractions, >100 chemicals were screened in each fraction. The substances with LC50 < 1000 mg/L were listed as toxic substances, and the number of toxic substances dominated the toxicity of urban rivers. Our study highlights toxicity as a comprehensive indicator for assessing river pollutants and reveals relationship between the number of toxic substance and river toxicity. These findings have direct implications for the monitoring and management of environmental stressors and the protection of aquatic organisms and human health.

Structural simplification of Osimertinib to elaborate new indolyle-pyrimidine-5-carbonitrile derivatives with Anti-proliferative and Anti-SARS-CoV-2 activities assisted by molecular dynamic simulation

Based on the simplicity and modification of the medication osimertinib, two new series of indolyle-pyrimidine-5-carbonitrile scaffolds were created and synthesized with dual action as anti-SARS-Cov-2 and anticancer. The newly created heterocyclic compounds' chemical structures were effectively characterized. With IC50 values of 18.52, 20.89, and 19.85, respectively, compounds 9b, 10, and 15 had inhibitory actions against SARS-CoV-2 when compared to remdesivir and chloroquine, which served as pharmacological controls and had IC50 values of 3.38 μM and 24.9 μM, respectively.Furthermore, compounds 9a and 13 showed anti-proliferative activity against HepG2 cell lines with IC50s of 5.63 μM and 3.06 μM, respectively, in comparison to doxorubicin's IC50 of 7.4 μM. qRT-PCR revealed that HepG2 cells treated with compounds 9a and 13 showed increased p53 expression levels and decreased CDK1 and PI3K expression levels in comparison to doxorubicin. Molecular dynamics simulations of 20 ns duration were performed with PI3Kα, PI3Kγ, and CDK and active compound complexes. The results confirm that compound 13 has the potential to be a therapeutic candidate for additional preclinical and clinical research, as indicated by the molecular docking data.

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.

Investigation of Cytotoxic Effects of Tragopogon reticulatus Against HepG2 and MCF-7 Cell Lines and Antioxidant, Antimicrobial Effects Against Some Microorganisms

Plants have been used for various purposes throughout history. This subject has received increasing attention in the field of traditional medicine in recent years. Tragopogon reticulatus, as a forage grass plant in turkey, is a species that stands out with rich vitamin and mineral content. The aim of this study was to investigate the antimicrobial, antioxidant, and cytotoxic activities of T. reticulatus. Two separate extracts were prepared at different concentrations using hexane and methanol solvents obtained from the T. reticulatus plant, and cytotoxic activity was evaluated by the MTT Assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method on human liver cancer (HepG2) and human breast cancer (MCF7) cell lines. The antioxidant activity of the extracts obtained from methanol and hexane was determined by the DPPH (2,2-diphenyl 1-picrylhydrazyl) radical scavenging capacity method. Antimicrobial activity was evaluated by the disk diffusion method, and bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Bacillus megaterium, and Candida albicans fungus were used in the study. The hexane extract obtained from the T. reticulatus plant showed a high cytotoxic activity of 44% in the MCF7 cell line, while it showed a 51% dead cell count in the HepG2 cell line. When the antioxidant results were evaluated, it was determined that the DPPH radical scavenging effect of the hexane extract exhibited the most effective activity at 19%. When the antimicrobial results were evaluated, it was determined that the concentrations prepared with hexane exhibited the most effective activity with a zone diameter of 16 mm against B. megaterium. These findings suggest that T. reticulatus plant extracts can be considered as a potential source. These results may shed light on future research into the biological effects of the plant and contribute to the development of new treatment methods.

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

Development and Evaluation of Bis-benzothiazoles as a New Class of Benzothiazoles Targeting DprE1 as Antitubercular Agents.

Benzothiazole-bearing compounds have emerged as potential noncovalent DprE1 (decaprenylphosphoryl-β-d-ribose-2'-epimerase) inhibitors active against Mycobacterium tuberculosis. Based on structure-based virtual screening (PDB ID: 4KW5), a focused library of thirty-one skeletally diverse benzothiazole amides was prepared, and the compounds were assessed for their antitubercular activity against M.tb H37Ra. Most potent compounds 3b and 3n were further evaluated against the M.tb H37Rv strain by the microdilution assay method. Among the compounds evaluated, bis-benzothiazole amide 3n emerged as a hit molecule and demonstrated promising antitubercular activity with minimum inhibitory concentration (MIC) values of 0.45 μg/mL and 8.0 μg/mL against H37Ra and H37Rv, respectively. Based on the preliminary hit molecule (3n), a focused library of 12 more bis-benzothiazole amide derivatives was further prepared by varying the substituents on either side to obtain new leads and generate a structure-activity relationship (SAR). Among these compounds, 6a, 6c, and 6d demonstrated remarkable antitubercular activity with MIC values of 0.5 μg/mL against H37Ra and 1.0, 2.0, and 8.0 μg/mL against H37Rv, respectively. The most active compound, 6a, also displayed significant efficacy against four drug-resistant tuberculosis strains. Compound 6a was assessed for in vitro cytotoxicity against the HepG2 cell line, and it displayed insignificant cytotoxicity. Furthermore, time-kill kinetic studies demonstrated time- and dose-dependent bactericidal activity of this compound. The GFP release assay revealed that compound 6a targets the inhibition of a cell wall component. SNPs in dprE-1 gene assessment revealed that compound 6a binds to tyrosine at position 314 of DprE1 and replaces it with histidine, causing resistance similar to that of standard TCA1. In silico docking studies further suggest that the strong noncovalent interactions of these compounds may lead to the development of potent noncovalent DprE1 inhibitors.

Mitigation of methylglyoxal-induced hepatotoxicity by Boerhavia diffusa L. aerial extract: Insights from cellular and animal models

BackgroundBoerhavia diffusa (Punarnava), is a perennial herb with a long-standing reputation for its antioxidative and anti-inflammatory properties, dating back to ancient times. Methylglyoxal is an advanced glycation end-product, known to be toxic in liver cell line as well as in mice model. Our objective is to illustrate the protective action of punarnava aerial extracts in methylglyoxal-induced hepatotoxicity in cell line and mice model. MethodsPunarnava aerial parts were collected and different solvent extracts were prepared in methanol, dichloromethane and hexane by maceration followed by their LCMS/MS characterization, determination of total phenolic, total flavonoid contents and antioxidant activity by DPPH reagent. Cell viability of the extracts and methylglyoxal was assessed using different cell lines. In vitro protective effect of punarnava methanolic extract (PME) against methylglyoxal was evaluated by cell migration assay, NO and ROS production assays and Oil Red O staining in HepG2 cell line. BALB/c mice were pretreated with Punarnava methanolic extract (200 mg/kg and 400 mg/kg) for seven days followed by 290 mg/kg methylglyoxal administration for 6 hrs to induce hepatotoxicity. Serum glucose, AST, ALT, ALP and GSH level were checked and liver histopathological damages were identified. ResultsAmong the three Punarnava extracts, PME possessed maximum antioxidant, total phenolic and flavonoid content as well as least cytotoxic to liver cell line. Methylglyoxal showed maximum toxicity in HepG2 cells with IC50 (50 % inhibitory concentration) 3 µM. PME confers protection against methylglyoxal-induced cytotoxicity by decreasing ROS, promoting cell migration and preventing loss of cell viability. No significant change was observed in NO production and Oil Red O staining. PME-treated mice showed decrease in liver ALP levels and glucose with intact cellular morphology compared to hepatocyte steatosis and nuclear degeneration in methylglyoxal-treated group. DiscussionsIndigenous herb Punarnava is effective in protecting liver cells from damage induced by the glycolytic byproduct, methylglyoxal.