HeLa Cancer Cell Lines Research Articles

Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines

ABSTRACT Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5’ CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.

Dihydroaurones and Isoflavan Derivatives from the Roots of Glycyrrhiza asymmetrica.

As a continuation of our pharmacognostic studies on different Glycyrrhiza species growing in Türkiye, the phytochemical investigation of the roots of Glycyrrhiza asymmetrica Hub.-Mor., a licorice species endemic to Türkiye, was carried out. This study yielded twenty-three secondary metabolites (1-23) including nine previously unreported compounds: two dihydroaurone-3-enoic acids, licoaurone A (1) and licoaurone B (2), isoflavan hydroxypreglabridin (3), isoflavanone cyclodeoxykievitone (4), flavanone-3-ol glycyasymmetrol (5), and four bi-isoflavans, glycyasymmetrica A-D (6-9). The structures of isolated compounds were established by NMR and MS experiments. The relative configurations (6-9) were assigned by a combined quantum mechanical/NMR approach, comparing the experimental 13C/1H NMR chemical shift data and the related predicted values. The absolute configurations of compounds 1-9 were assigned by comparison of their experimental electronic circular dichroism curves with the TDDFT-predicted curves. All isolated compounds were also evaluated for their cytotoxic activity against MCF-7, HeLa, HepG2, and A549 cancer cell lines by using MTT assay.

Synthesis of chitosan and carboxymethyl cellulose connect flavonoid (CH-Fla-CMC) composite and their investigation of antioxidant, cytotoxicity activities.

This study successfully synthesised and characterised composites combining chitosan (CH), carboxymethyl cellulose (CMC), and various flavonoids (Fla). This innovative approach demonstrates the potential for developing functional materials with antioxidant and food preservation properties. The composites CH-Fla-CMC (1-5) was characterised using advanced techniques such as FT-IR, UV-Vis, XRD, SEM, TEM, and TGA, providing robust data on their structural, morphological, and thermal properties. CH-connected CMC has been used to prevent many diseases, based on the findings of this study. Therefore, dietary flavonoids (Fla = 1. 3-Hydroxyflavone; 2. rhamnetin; 3. natsudaidain; 4. isorhamnetin; 5. myricetin) was used to prepare the composites in this study. Dietary flavonoids play an important role in the prevention of degenerative diseases. In addition, oxygen permeability (OP), water solubility (WS), and moisture content (MS) were analysed. The synthesised composites were screened for antioxidant and cytotoxic activities. Multiple antioxidant assays (DPPH, H₂O₂, NO, ABTS•⁺, and AAPH) were conducted, confirming the superior radical scavenging activity of CH-Fla-CMC-5 compared to standards such as BHT and Trolox. The synthesised composite CH-Fla-CMC 5 was more active than the standard butylated hydroxytoluene (BHT) against 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), and nitric oxide (NO) radical scavenging activity (DPPH: 10.30 vs. 33.88 μg/mL; H2O2: 13.26 vs. 27.16 μg/mL, and NO: 13.56 vs. 31.73 μg/mL), whereas 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS•+) decolourisation assay and lipid peroxidation method (AAPH) CH-Fla-CMC 5 was more active than the standard Trolox (ABTS: 91.26 ± 0.59 % vs. 85.28 ± 0.97 %; AAPH: 91.02 ± 0.01 % vs. 62.39 ± 0.35 %). The synthesis and characterisation methods are laboratory-based. This study primarily focused on in vitro antioxidant and cytotoxicity assays. The performance of these composites in living organisms and real-life food packaging scenarios remains untested. Cytotoxicity against only check these cell lines such as MCF-7, HeLa, HepG2, and normal Vero cancer cell lines was assessed. Only five flavonoids were tested, potentially limiting the generalisability of the findings to other dietary flavonoids. In the future, we plan to compare more cell lines with flavonoids. These laboratory-based methods have been converted into industrial production. The CH-Fla-CMC-5 composite performed better than the other compounds in all tests. Based on our findings, the synthesised CH-Fla-CMC-5 composite could be used to pack dishes that are watery, acidic, or alcoholic, as well as to coat freshly cut fruits.

Probing structural requirements for thiazole-based mimetics of sunitinib as potent VEGFR-2 inhibitors.

Novel thiazole analogs 3a, 3b, 4, 5, 6a-g, 8a, 8b, 9a-c, 10a-d and 11 were designed and synthesized as molecular mimetics of sunitinib. In vitro antitumor activity of the obtained compounds was investigated against HepG2, HCT-116, MCF-7, HeP-2 and HeLa cancer cell lines. The obtained data showed that compounds 3b and 10c are the most potent members toward HepG2, HCT-116, MCF-7 and HeLa cells. Moreover, compounds 3a, 3b, 6g, 8a and 10c were assessed for their in vitro VEGFR-2 inhibitory activity. Results proved that compound 10c exhibited outstanding VEGFR-2 inhibition (IC50 = 0.104 μM) compared to sunitinib. Compound 10c paused the G0-G1 phase of the cell cycle in HCT-116 and MCF-7 cells and the S phase in HeLa cells. Additionally, compound 10c elevated caspase-3/9 levels in HCT-116 and HeLa cells, leading to cancer cell death via apoptosis. Furthermore, compound 10c showed a significant reduction in tumor volume in Swiss albino female mice as an in vivo breast cancer model. Docking results confirmed the tight binding interactions of compound 10c with the VEGFR-2 binding site, with its binding energy surpassing that of sunitinib. In silico PK studies predicted compound 10c to have good oral bioavailability and a good drug score with low human toxicity risks.

Synthesis and Anticancer Evaluation of O-Alkylated (E)-Chalcone Derivatives: A Focus on Estrogen Receptor Inhibition.

Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of O-alkyl (E)-chalcone derivatives (4a-4v) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry. In vitro cytotoxicity assays revealed varying effectiveness, with compounds 4a, 4b, 4q, and 4v exhibiting potent activity against MDA-MB-231 and MCF-7, showing IC50 values between 2.08 and 13.58 µM, besides HCT-116 and HeLa cancer cell lines (IC50 values between 6.59 and 22.64 µM). Notably, compound 4b displayed remarkable selectivity, with an IC50 of 54.59 µM against the non-cancerous WI-38 cell line. Additionally, protein kinase inhibition assays indicated that compounds 4b and 4q effectively inhibited EGFR and VEGFR-2, with 4b outperforming the standard inhibitor erlotinib. Molecular docking studies of compound 4q showed strong binding affinities in the ATP-binding pockets of EGFR, HER2, VEGFR2, and CDK2. In silico analyses further highlighted the favorable pharmacokinetic properties of compound 4q, underscoring its potential as a selective tyrosine kinase inhibitor. These findings suggest the therapeutic promise of O-alkyl (E)-chalcone derivatives in cancer treatment.

RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

Rapid Assembly of 1,3-Dicarbonyl Fused 5-phenyl-1-Azabicyclo[3.1.0]hexanes and Their Cytotoxic Activities.

Synthesis of complex, multiring, spirocyclic, 1,3-dicarbonyl fused, and highly functionalized 5-phenyl-1-azabicyclo[3.1.0]hexanes (ABCH) has been achieved by an intermolecular reaction of 2-(2'-ketoalkyl)-1,3-indandiones or α,γ-diketo esters with (1-azidovinyl)benzenes under transition metal-free conditions. The reaction proceeds in a highly diastereoselective manner with a wide range of functional groups and provides moderate to good yields. Additionally, we have studied the preliminary biological activities of a few synthetic compounds against HeLa and triple-negative breast cancer (TNBC) cell lines.

In-vitro, In-silico Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.

Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities. To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing in-vitro and in-silico methods. Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins. The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3). Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC50 values were 82.9 μg/ml (LLSD-5), 162.3 μg/ml (LLSD-7), and 20.15 μg/ml (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action. The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both in-vitro and in-silico analyses support the potential of these metabolites as anticancer agents.

Alkaloids and Iridoids From Phlogacanthus curviflorus.

Four unreported pyridine alkaloids, curviflorines A-D (1-4), two undescribed iridoids, curviridoids A and B (5 and 6), and one known iridoid glycoside (7), were isolated from the twigs and leaves of Phlogacanthus curviflorus. The structures of these compounds were established by detailed interpretation of MS and NMR data, with the absolute configurations being assigned via comparison of experimental and calculated electronic circular dichroism spectra. Notably, it is the first report of alkaloidal constituents (1-4) from the genus Phlogacanthus. Compounds 1-7 did not show obvious inhibitory activities against α-glucosidase and NO production (in RAW264.7 macrophages), nor did they exhibit anti-oxidant activity and cytotoxicity towards MDA-MB231, A549 and HeLa cancer cell lines. Nevertheless, alkaloids 1-4 did exert a significant suppressing effect on TGF-β1-induced upregulation of the fibrotic marker protein fibronectin in HK-2 cells, indicating their antifibrotic potential.

Isolation, cytotoxicity evaluation, and molecular docking of 3,4,3’-tri-O-methylflavellagic acid from Anogeissus leiocarpus (DC.) Guill. & Perr. root

Cancer kills about 10 million people every year. Medicinal plants remain a major source in the global search for anticancer drugs. In this study, 3,4,3’-tri-O-methylflavellagic acid (MFA) was isolated from the methanol root extract of Anogeissus leiocarpus. The structure was determined by 1D- and 2D-NMR data. The cytotoxic effects of MFA were evaluated against human breast (MCF-7), colorectal (Caco-2), and cervical (HeLa) cancer cell lines using the 3-[4,5-dimethylthiazole-2-yl] 3,5-diphenyltetrazolium bromide assay. A multi-protein target screening via molecular docking was conducted against ten cancer-related proteins, and ADMET properties were evaluated. MFA exhibited the most potent activity against Caco-2 (IC50: 46.75 ± 13.00 µM). Molecular docking analysis showed that MFA had a strong binding affinity for the colchicine-binding site of αβ-tubulin and polo-like kinase-1 (binding energies: −8.5 and −8.4 kcal/mol, respectively). MFA also satisfied the Lipinski’s Rule of Five. MFA could, therefore, potentially serve as a scaffold for developing new anticancer molecules.

Fabrication of novel AIE active chemosensor for selective detection of Pd(II) and picric acid: extended detection in HeLa cancer cell line

The development, identification, and chemosensing activity of a Schiff base chemosensor (E)-2-(2-((5-bromo-2-hydroxybenzylidene)amino)propyl)-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xanthen]-3-one(RBSB). Simply condensing 5-bromo salicylaldehyde and rhodamine-1,2 diamino propane derivative (RBN) yields the Schiff base RBSB. Numerous spectroscopic, scanning...

Green synthesis of Au-Pt bimetallic nanoparticels using Croton caudatus Geisel leaf extract and their biological studies

Metal nanoparticles have a lot of interesting characteristics, and the field of medicinal applications may benefit significantly from them. In this investigation, gold-platinum (Au-Pt) bimetallic nanoparticles were synthesized employing leaf extract from Croton Caudatus Geisel. Utilizing transmission electron microscopy (TEM) examination and powder X-ray diffraction, the size of the synthesized nanoparticles was found to be between 12 and 33 nm. Using Debye Scherrer equation, particle size of the synthesized nanoparticle is determined and also consistent with transmission electron microscopy (TEM) analysis. The materials tend to be rectangular-shaped. This is a single-step, green protocol that does not employ any capping or reducing agents. The bio-active compounds in leaf extract act as reducing/capping/stabilizing agents and also fabricated with surface of the nanoparticles. Since green synthesis is an easy, stable, quick, low-cost, and environmentally friendly process, it opens up new possibilities for the synthesis of nanoparticles. Bimetallic nanoparticle synthesis generally involves mixing two different aqueous metal solutions with a natural reducing agent, like a plant extract. It has been proposed that plant phytochemicals with reducing or antioxidant properties reducemetal ions into metal nanoparticles. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) analysis, Fourier-transform infrared (FT-IR) spectroscopy, and ultraviolet (UV) spectroscopy were all utilized to completely characterize the synthesized nanoparticles. It has been found that biological studies exploring in vitro antibacterial, in vitro antifungal, and anti-cancerous activity showed significant implications. In accordance with study results, the synthesized nanomaterialshad a strong cytotoxic effect on HeLa cancer cell lines, with an MTT assay IC50 value of 37.17 μg/ml/24 h.

New derivatives based on zerumbone scaffold as anticancer inhibitors: Synthesis, in vitro anticancer evaluation, docking, and MD simulation studies

A three-step procedure was applied to synthesize seven novel zerumbone ethers 7a–g with N-(4-hydroxybenzyl) benzamide, N-(4-hydroxybenzyl) substituted benzamide, and N-(4-hydroxybenzyl) cinnamamide moieties, including simultaneous O- and N-acylations, ester hydrolysis, and O-alkylation. The structure of intermediates and target compounds was elucidated using one-dimensional and two-dimensional nuclear magnetic resonance, and high-resolution mass spectrometry data. Their cytotoxic activities were screened on three human cancer cell lines HepG2, LU-1, and HeLa. The results showed that ethers 7a–g exhibited activity against all tested cell lines with IC50 values ranging from 1.71 to 6.86 µM and stronger than zerumbone, approximately 10–35 folds. Theoretically, the mode of their anticancer action was studied based on predicting the ability to inhibit Fibroblast Growth Factor Receptor 1 and Vascular Endothelial Growth Factor Receptor 2 proteins using docking and molecular dynamic simulation studies. The interaction of 7a–g with important amino acids in the active binding sites of protein Fibroblast Growth Factor Receptor 1 and Vascular Endothelial Growth Factor Receptor 2, and Umbrella Effect formation explained the significant improvement in their cytotoxic activities compared to the parent compound zerumbone.

Liquid phase preparation and characterization of MgO nanoparticles and their butchery activities against dental bacterial pathogens and human cervical cancer cell line.

A novel method for synthesizing nanomaterials involves microbial or phytochemical nano-factories, which offer an eco-friendly, cost-effective, and reliable approach to producing clean and reproducible products. In this study, magnesium oxide nanoparticles (MgO NPs) were synthesized using Avicennia marina, a marine plant, as both a nucleation and stabilizing agent. The MgO NPs were characterized for crystallinity, cut-off wavelength, morphology, thermal stability, and surface properties using XRD, EDX, BET, UV-Visible spectroscopy, DLS, zeta potential analysis, SEM, TEM, TGA/DTA, and PL spectroscopy. Using the Brunauer-Emmett-Teller (BET) method, the specific surface area of the MgO nanoparticles was determined to be 97.248m2/g. The optical band gap energy of the MgO nanoparticles that corresponded to the highest absorption peak was determined to be 5.8eV. Additionally, the antimicrobial, scavenging, and antioxidant activities of the MgO NPs were evaluated against dental bacterial pathogens. To explore anticancer potential, the MgO NPs were tested on a cervical cancer cell line (HeLa) using an MTT assay, which revealed that cytotoxicity increased with higher MgO NP concentrations. MgO nanoparticles were applied at concentrations of 25μg/mL, 50μg/mL, 75μg/mL, and 100μg/mL to inhibit the proliferation of cancer cell lines. The cytotoxicity observed at an IC50 concentration of 56.54μg/mL is primarily influenced by factors such as the small size, increased surface-to-volume ratio, oxygen vacancies, and the morphology of the nanoparticles. This interdisciplinary study contributes to the understanding of MgO NPs and their multifunctional potential in combating dental infections and cervical cancer.

Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects.

A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides 5 and 10 were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or l-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides 5 and 10 were used for the synthesis of 13-23, the derivatives of moronic acid (11) and morolic acid (12), to get a series of amide derivatives of the less frequently studied triterpenoids 11 and 12. The target compounds, and their intermediates, were subjected to an investigation of their antimicrobial, antiviral and cytotoxic activity. Selectivity of the pharmacological effects was found. Generally, the target compounds inhibited only the G+ microorganisms. Compound 16 inhibited Staphylococcus aureus (I = 99.6%; c = 62.5 μM) and Enterococcus faecalis (I = 85%; c = 250 μM). Several compounds showed moderate antiviral effects, both anti-HIV-1, 19 (EC50 = 57.0 ± 4.1 μM, CC50 > 100 μM), 20 (EC50 = 17.8 ± 2.1 μM, CC50 = 41.0 ± 5.2 μM) and 23 (EC50 = 12.6 ± 0.82 μM, CC50 = 38.0 ± 4.2 μM), and anti-HSV-1, 22 (EC50 = 27.7 ± 3.5 μM, CC50 > 100 μM) and 23 (EC50 = 30.9 ± 3.3 μM, CC50 > 100 μM). The target compounds showed no cytotoxicity in cancer cells, however, several of their intermediates were cytotoxic. Compound 21 showed cytotoxicity in HeLa (IC50 = 7.9 ± 2.1 μM), G-361 (IC50 = 8.0 ± 0.6 μM) and MCF7 (IC50 = 8.6 ± 0.2 μM) cancer cell lines, while being non-toxic in normal fibroblasts (BJ; IC50 > 50 μM).

ANTIOXIDANT AND In-vitro CYTOTOXIC ACTIVITY OF TYPICAL ACEHNESE PLANTS AGAINST HUMAN CERVICAL CANCER (HeLa) CELL LINE AND THEIR PHYTOCHEMICAL PROPERTIES

Michelia Alba (M. Alba) plant is one of the typical Acehnese plants that has a lot of bioactivity and potential as a basic ingredient for drug manufacture. The aim of this study was to determine the phytochemical properties, antioxidant and in vitro cytotoxic activity of M. Alba leaves and flowers against the human cervical cancer (HeLa) cell line. This research was conducted by maceration method, where dry samples were soaked with ethanol solvents, and then crude ethanol extract was tested for antioxidant and in vitro cytotoxic activity against the HeLa cell line. The results of phytochemical properties showed leaves and flowers of M. alba contained secondary metabolites including alkaloids, terpenoids, flavonoids, tannins, and saponins. Antioxidant testing using DPPH solution of M. alba leaves showed IC50 value was 81.99 and for flowers was 30.18, this result indicates that M. alba flowers have very strong antioxidant activity, while the leaves have weak activity. The results of the cytotoxic test on the HeLa cell line from M. alba leaves and flowers showed very active where the CD50 values were 4 ppm and 2 ppm, respectively.

Lauryl-NrTP6 lipopeptide self-assembled nanorods for nuclear-targeted delivery of doxorubicin.

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH2 (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer. DX is trapped in the peptide regions of the assemblies. Confocal laser scanning microscopy shows that the peptide assemblies translocate into the nucleus. Cytotoxicity studies over 72 h in A549 and HeLa cancer cell lines show less toxicity for the LP encapsulated DX than for free DX. In contrast, subtoxic doses of encapsulated DX are more effective than free DX in avoiding colony formation over 14 days, with a complete absence of colonies for the LP-encapsulated DX. The results show a more efficient and slow delivery of DX to the nucleus through LP encapsulation, paving the way for the use of lower DX doses as a chemotherapeutic agent.

Synthesis and antiproliferative evaluation of novel chrysin selenocyanates

Selenocyano fragments with distinct structural characteristics were successfully incorporated into the 5- and 7-positions of chrysin via etherification and esterification of its hydroxyl groups. Eleven novel chrysin selenocyanates were synthesized, and their structures characterized by NMR and HRMS. The activities of all compounds were evaluated against human cervical cancer cell lines HeLa, ovarian cancer cell lines SKOV-3, and breast carcinoma cell lines MCF-7 using MTT assays. Results indicated that esterified chrysin derivatives significantly inhibited HeLa cells, while alkylated chrysin ethers showed notable activity against SKOV-3 and MCF-7 cells. Compounds 5c and 5e exhibited the strongest inhibitory effects on SKOV-3 cells, with IC50 values of 2.27 ± 0.19 μM and 2.51 ± 0.33 μM, respectively. The introduction of diselenocyanate at both the 5- and 7-positions demonstrated superior inhibitory activity compared to a single selenocyanate at the 7-position alone. The findings may aid in designing novel chemotherapeutic drugs.

Synthesis of Novel Benzofuran Spiro-2-Pyrrolidine Derivatives via [3+2] Azomethine Ylide Cycloadditions and Their Antitumor Activity.

A synthetic strategy of a three-component spiro-pyrrolidine compound based on benzofuran via an [3+2] azomethine ylide cycloaddition reaction is reported herein. Under mild optimal conditions, this reaction can quickly produce potentially bioactive compounds with a wide range of substrates, high yield, and simple operation. The desired products were obtained with a yield of 74-99% and a diastereomeric ratio (dr) of >20:1. Subsequently, the inhibitory effects of the compounds on the cell viability of the human cancer cell line HeLa and mouse cancer cell line CT26 were evaluated. Compounds 4b (IC50 = 15.14 ± 1.33 µM) and 4c (IC50 = 10.26 ± 0.87 µM) showed higher antiproliferative activities against HeLa cells than cisplatin (IC50 = 15.91 ± 1.09 µM); compounds 4e (IC50 = 8.31 ± 0.64 µM) and 4s (IC50 = 5.28 ± 0.72 µM) exhibited better inhibitory activities against CT26 cells than cisplatin (IC50 = 10.27 ± 0.71 µM). The introduction of electron-donating substituents was beneficial to the inhibitory activities against cancer cells. Molecular docking simulations revealed that 4e and 4s may exert corresponding bioactivities by binding to antitumor targets through hydrogen bonds, providing a new approach for discovering spiro-heterocyclic antitumor drugs.

Novel Copper(II) Coordination Compounds Containing Pyridine Derivatives of N4-Methoxyphenyl-Thiosemicarbazones with Selective Anticancer Activity.

Ten coordination compounds, [Cu(L1)Cl] (C1), [Cu(L1)NO3] (C2), [Cu(L2)Cl] (C3), [Cu(L2)NO3] (C4), [Cu(L3)Cl] (C5), [Cu(L3)NO3] (C6), [Cu(L4)NO3] (C7), [Cu(L4)Cl] (C8), [Cu(L5)Cl] (C9), and [Cu(L5)NO3] (C10), containing pyridine derivatives of N4-methoxyphenyl-thiosemicarbazones were synthesized and characterized. The molecular structure of four compounds was investigated using single crystal X-ray diffraction. Spectral analysis techniques such as FT-IR, 1H NMR, 13C NMR, elemental analysis, and molar conductivity were used for all the synthesized compounds. The tested synthesized compounds were evaluated for their anticancer activity and selectivity against a variety of cancer cell lines, including HL-60, LNCaP, MCF-7, HepG-2, K-562, HeLa, BxPC-3, RD, and MDCK normal cell line. Most compounds demonstrated selective anticancer activity superior to doxorubicin. Notably, all ligands showed high antiproliferative activity against HL-60 cells, with IC50 values between 0.01 and 0.06 µM and a selectivity index as high as 5000. Coordination of copper(II) with ligands HL1 and HL3 notably enhanced antiproliferative activity, lowering the IC50 to 0.03 µM. Additionally, the antioxidant activity of these compounds was assessed, revealing that all tested ligands and most coordination compounds exhibited greater antioxidant activity compared to Trolox, with some ligands showing activity up to 12.3 times higher. Toxicity studies on Daphnia magna indicated low toxicity for the ligands, generally less than doxorubicin, with LC50 values ranging from 13 to 90 µM, suggesting moderate toxicity. Conversely, the coordination complexes were more toxic, with LC50 values between 0.5 and 13 µM.