HepG2 Cancer Cell Lines Research Articles

Anticancer potential of folic acid functionalized Ag-Zn bimetallic nanoparticles

In the current study, silver-zinc bimetallic nanoparticles (BNPs) have been synthesized using folic acid (FA) for investigating their potential against HepG-2 cancer cell lines. These FA-Ag/Zn BNPs were prepared and characterized using different techniques. UV/Vis analysis indicated absorbance peaks at 360 nm and 440 nm confirming the presence of BNPs. FTIR analyses confirmed the formation of FA-Ag/Zn BNPs and SEM images revealed a grain-like morphology which is uniformly distributed throughout with a particle size of 65.22 nm. The XRD diffractogram revealed crystal structure of the said BNP’s as face-centered cubic (FCC) having a crystallite size of 23.29 nm. Synthesized nanoparticles (FA-Ag/Zn BNPs) were then tested for their anticancer potential i.e. cellular mitochondrial activity was measured using MTT assay with varied concentration of the synthesized BNPs from 10 to 400 µg/mL. Maximum cytotoxicity (CTY) was recorded for 400 µg/mL of BNPs showing a significant cytotoxicity against HepG-2 cells as compared to the control. The current study may be considered as a significant in providing alternative route for chemotherapy. This route would be much safer, cost-effective and feasible due to the production of reactive oxygen species (ROS) which eventually result in death of cancerous cells.

New Tin (IV) and Organotin (IV) Complexes with a Hybrid Thiosemicarbazone/Hydrazone Ligand: Synthesis, Crystal Structure, and Antiproliferative Activity.

Nowadays, the search for new chemotherapeutic agents with low toxicity and high selectivity is a major concern. In this paper, we report the synthesis and characterization of a hybrid thiosemicarbazone/hydrazone ligand in its neutral form (L1H2) and as the chloride salt ([L1H3]Cl)-, three diorganotin (IV) complexes, and one complex with Sn (IV). The compounds have been fully characterized by IR, mass spectra, 1H, 13C, and 119Sn NMR, 119Sn CP/MAS NMR, and by single crystal X-ray diffraction. The organotin compounds have the empirical formula [SnR2L1] (R = Me, Bu, and Ph), but in the solid state, they are polymeric species with seven coordination number due to weak coordination of the pyridine nitrogen, whereas in solution, the polymeric structure is lost to afford hexacoordinate monomeric species. Reaction with SnI4 yields complex [Sn (L1)2]·EtOH, with the metal in a distorted dodecahedral arrangement. We have evaluated the antiproliferative activity of the two forms of the ligands and the four coordination compounds against MDA-MB-231, HeLa, PC3, and HepG2 cancer cell lines, and WI-38 normal cell line, and all the compounds present higher activity than cisplatin, used as the standard control. To investigate the mode of action, we have selected the most active complex, containing phenyl substituents, and used the triple negative breast cancer cell line MDA-MB-231. The results show that the complex induces apoptotic cell death promoted by generation of reactive oxygen species and by disruption of mitochondrial membrane potential.

Phenolic profiling and bioactivity assessment of in vitro propagated Psidium cattleianum Sabine: A promising study

Psidium cattleianum Sabine (strawberry guava) is an evergreen shrub that is grown as a fruiting hedge and has received significant consideration in the food and pharmaceutical disciplines. This study aims to set a promising protocol for in vitro propagation of P. cattleianum, along with profiling the phenolic content of the original plant (OP), induced callus (IC), and regenerated plantlets (RP) extracts, ultimately, evaluating their anti-inflammatory, antioxidant, and anticancer potential. Seeds were treated with commercial bleaching, HCl, and H2O2 to enhance the germination percentage and minimize the contamination percentage. Culturing sterilized leaf explants onto Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA), 2,4-dichloro phenoxy acetic acid, and kinetin showed the best callus induction, while supplementation of MS media with BA, adenine sulfate, naphthalene acetic acid, and gibberellic acid activated regeneration. Augmentation of MS media with indol-3-butyric acid recorded the maximum rooting percentage. Finally, the obtained rooted shoots were successfully acclimatized in sand and peat moss soil. HPLC-MS/MS profiles of OP, RP, and IC showed a variety of phenolic metabolites. IC extract decreased the viability of MCF-7, HepG2, and K-562 cancer cell lines. Also, OP exhibits strong antioxidant activity. P. cattleianum and its RP are profound sources of phenolic compounds promoted for promising applications in the food and pharmaceutical industries.

Recovery of Cembratrien-Diols from Waste Tobacco (Nicotiana tabacum L.) Flowers by Microwave-Assisted Deep Eutectic Solvent Extraction: Optimization, Separation, and In Vitro Bioactivity.

Deep eutectic solvents (DESs) are novel solvents with physicochemical properties similar to those of ionic liquids, and they have attracted extensive attention for the extraction of bioactive compounds from different plant materials in the context of green chemistry and sustainable development. In this study, seven DESs with different polarities were explored as green extraction solvents for cembratrien-diols (CBT-diols) from waste tobacco flowers. The best solvent, DES-3 (choline chloride: lactic acid (1:3)), which outperformed conventional solvents (methanol, ethanol, and ethyl acetate), was selected and further optimized for microwave-assisted DES extraction using the response surface methodology. The maximum yield of CBT-diols (6.23 ± 0.15 mg/g) was achieved using a microwave power of 425 W, microwave time of 32 min, solid/liquid ratio of 20 mg/mL, and microwave temperature of 40 °C. Additionally, the isolated CBT-diols exhibited strong antimicrobial activity against Salmonella, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa and antitumor activity in the human liver cancer HepG2 and SMMC-7721 cell lines. This study highlights the feasibility of recovering CBT-diols from tobacco flower waste using DESs and provides opportunities for potential waste management using green technologies.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral Lemnalia bournei.

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 μM.

Investigation of Antioxidant, Antimicrobial and Cytotoxic Activity of Cydonia oblonga Leaf on Breast Cancer (MCF-7) and Liver Cancer (HepG2) Cell Lines

Cancer, one of the most common pathologies in the world, has been reducing the standard of living of many people for centuries and can cause death. Many medicinal plants are widely used in cancer treatment due to their ability to improve disease symptoms and low side effects. Cydonia oblonga (C. oblonga) leaf, which is among the medicinal plants and has important health properties, is a type of plant commonly known as quince leaf. Although it originates from Asia, it is cultivated in many countries today. In this study, antioxidant, antimicrobial and cytotoxic activities of C. oblonga leaves on MCF-7 and HepG2 cell lines were investigated. As a method, the collected C. oblonga leaves were extracted in methanol and hexane solvents. The extracts were tested on MCF-7 and HepG2 cell lines using MTT Assay method for cytotoxic activity, DPPH method for antioxidant activity and well agar method for antimicrobial effects of the extract on five different microorganisms. As a results, although C. oblonga leaf in both cell lines hexane extract exhibited stronger cytotoxic activity than methanol extract, methanol extract was found to have stronger antioxidant effect than hexane extract. The extracts applied to microorganisms showed the best zone diameter effect on E. coli and the lowest effect on B. megaterium. In addition, it was observed that C. oblonga leaf has stronger antimicrobial effects than anticancer and antioxidant activity.

A green chemistry approach for preparation of metronidazole-zinc (ІІ) complexes: In vitro characterization, antimicrobial activity and promising cytotoxicity

Antibiotic-metal complexes attract the attention of pharmaceutical scientists who endeavor to increase the activity of antibiotics currently in use as those looking for new compounds possessing modified pharmacological and toxicological properties. This research proposed enhanced antimicrobial and cytotoxic activities of metronidazole and reduced irritancy of zinc chloride through complexation. The chemically green preparation of metronidazole: zinc (ІІ) complexes with different ratios: (A; 2:1), (B; 1:1) and (C; 1:2), revealed the formation of three complexes. The differences between their structures, physical and chemical properties were evaluated using morphological characteristics, DSC, XRD, FTIR, Mass spectrometry, and UV–Vis spectroscopy. The antimicrobial activities of the complexes were increased when compared to the parent drug where complex-C manifested the highest antibacterial activity (MIC = 0.625 mM and 10 mM for the bacterial strains and C. albicans, respectively). The antitumor efficacy of the complexes was studied against HepG2 and MCF-7 human cancer cell lines. Complex-A showed the highest cytotoxicity against HepG2 cells (IC50 = 17.2 μM), while, complex-C displayed the most cytotoxic activity against MCF-7 cells (IC50 = 29.0 μM). The in vivo skin irritancy study of the complexes on rats and their histological examination were assessed and showed no erythema and/or edema. Our results suggest the promising antimicrobial and antitumor activity of the prepared metronidazole-zinc complexes.

New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies

BackgroundVEGFR-2 has emerged as a prominent positive regulator of cancer progression. AimDiscovery of new anticancer agents and apoptotic inducers targeting VEGFR-2. MethodsDesign and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. In silico investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed. ResultsCompound 15 showed the strongest VEGFR-2 inhibitory activity with an IC50 value of 0.066 μM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC50 values ranging from 0.04 to 4.71 μM, relative to sorafenib (IC50 = 2.24 ± 0.06 and 3.17 ± 0.01 μM against HepG2 and MCF-7, respectively). Also, compound 15 showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound 15 showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound 15 had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound 15 in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound 15 to interact with VEGFR-2. ConclusionCompound 15 has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer.

Evaluation of anticancer effect of Cladophora glomerata algae extract

Cladophora glomerata has numerous biologically active properties and is considered one of the most essential medicinal algae. The purpose of this research was to investigate the anticancer efficacy of Cladophora glomerata algae extract against human hepatocellular carcinoma (HepG2), human cervical carcinoma (HeLa), and normal mouse embryonic fibroblast (MEF) cell lines. The needed algae was found in the Hassan Al-Hamoud River , Baquba, Iraq. The chemical detection of some chemical components of the ethanolic extract of C. glomerata revealed that the extract contains a group of active compounds. The study showed significant variation (p<0.05) among inhibition percentages of cancer cell line HepG2, Hella, and MEF cell lines that were treated with different concentrations (15.1, 31.2, 62.5, 125, 250, 500, and 1000) μg/ml of C. glomerata extract. The outcomes showed that increased inhibition percentages of the above cell line were associated with increased concentrations. The inhibition percentage of HepG2, Hella, and MEF cell lines were 1.6 ± 30.88, 1.7 ± 14.10, and 1.2 ± 2.31 at concentration 15.1 (mg/ml), and was 3.8 ± 84.90, 3.6 ± 88.29, and 3.9 ± 23.2, respectively at concentration 1000 (mg/ml). The study concluded that the C. glomerata extract with different concentrations significantly inhibited cancer cell lines (HepG2 and Hela) and ME because they have antiproliferative and antioxidant activity against cancers. The extract's inhibitory impact begins at low doses and increases with increasing concentration. The study would be beneficial to use macroalgae as new and sustainable sources of bioactive compounds against cancer.

Anti-oxidant and cytotoxic activity of Spirulina platensis ethanolic extract against Caco-2 and HepG2 cancer cell lines

Spirulina platensis is blue-green algae received significant attention for its high nutritional value, it is a source of powerful antioxidants. The cytotoxicity of crude extract is not well recorded. The aim of current study to evaluate the cytotoxicity of S. platensis extracts on colon cancer (CaCo-2), hepatic cancer (HepG2) cell lines, normal fibroblast cells line (HdFn) and also antioxidant activity. The percent of 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity was determined for serial concentrations of extract ranging from 3.125 to 200 μg/ml. Cell lines were treated for 24 hours with different concentrations of extract ranging from 25 to 400 µg/ml. Cell viability testing using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay which determined how the extract affected caspase 9 activity. The results revealed that extract had moderate antioxidant activity, showing the DPPH scavenging activity reached 58% in a concentration of 200μg/ml, and IC50 was 95.84 μg/ml. The extract significantly decreased CaCo-2 cell viability with IC50 99.12 µg/ml, compared to HdFn viability with IC50 157.6 µg/ml. On CaCo-2 cells, the extract's cytotoxicity was more evident (P< 0.05) than HdFn cells. The extract had more significant (P<0.05) cytotoxicity on cancer cell lines and also significantly decreased the viability of HepG2 cells with IC50 167.4 µg/ml, than the viability of HdFn with IC50 214.9 μg/ml. The extract revealed significantly higher (P< 0.05) cytotoxicity against HepG2 cells than the normal HdFn cells. This study concluded that the extract exerted a dose-dependent anti-proliferation effect on CaCo-2 cells and HepG2 cells by comparing them with HdFn cells.

Design and synthesis of BMH-21-like quinazolinone derivatives as potential anti-cancer agents

In the present study, a new series of quinazolin-4(3H)-one based compounds was designed, synthesized, and biologically evaluated as potential anticancer. The 11-oxo-11H-pyrido [2, 1-b] quinazoline-6-carboxylic acid 3a-c was synthesized as a precursor to prepare the pyridoquinazolinecarboxamides derivatives with different amines (7a-e). The molecular structures of these novel compounds were characterized through the analysis of various spectroscopic methods. Following that, the antiproliferative activity of synthesized compounds was evaluated against HepG2, MCF7, and HT-29 cancer cell lines. Compound 8e, with an IC50 of 2.07 µM, demonstrated higher potency than doxorubicin (IC50=2.15±0.021 µM) against HepG2 cancer cells, while the potency of 8l against HepG2 (liver cancer) was comparable to Dox. The effect of 8e and 8l on the destruction of Pol I subunit of RPA194 was evaluated; 8e and 8l exhibited a reduction in RPA 194 compared to the control. The 8e induces 43.1 % and 8l 37.6 % of HepG2 cell deaths, with doxorubicin being 52 %. Molecular modeling studies show the good binding free energies ranged from -8.32 to -11.7 kcal/mol with a hexamer of the DNA double helix. Accordingly, our findings imply that these derivatives serve as promising precursors for the design of potent anticancer agents.

Phytochemical analysis and evaluation of its antioxidant, antimicrobial, and cytotoxic activities for different extracts of Casuarina equisetifolia.

Casuarina equisetifolia belongs to the Casuarina species with the most extensive natural distribution, which contain various phytochemicals with potential health benefits. This study aimed to investigate the chemical composition and biological activities of different extracts of Casuarina equisetifolia. The n-hexane extract was analyzed for its unsaponifiable and fatty acid methyl esters fractions, while chloroform, ethyl acetate, and butanol extracts were studied for their phenolic components. Six different extracts of C. equisetifolia needles were evaluated for their total phenolic content, total flavonoid content, and their antioxidant, antimicrobial, and cytotoxic activities. The n-hexane extract contained mainly hydrocarbons and fatty acid methyl esters, while ten phenolic compounds were isolated and identified in the chloroform, ethyl acetate, and butanol extracts. The methanolic extract exhibited the highest total phenolic and flavonoid content, highest antioxidant activity, and most potent cytotoxic activity against HepG-2 and HCT-116 cancer cell lines. The ethyl acetate extract showed the most significant inhibition zone against Staphylococcus aureus and Bacillus subtilis. Casuarina equisetifolia extracts showed promising antioxidant, antimicrobial, and cytotoxic activities. Overall, Casuarina equisetifolia is a versatile tree with a variety of uses, and its plant material can be used for many different purposes.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-β-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

A new cucurbitane − type triterpenoid from the bark of Elaeocarpus hygrophilus Kurz.

A new cucurbitacin, 3β-(β-D-glucopyranosyloxy)-5β,6β:16α,23α-diepoxycucurbit-24-en-11-one or hygrocucurbin A (1), along with two known compounds, including 3β-(β-D-glucopyranosyloxy)-16α,23α-epoxycucurbita-5,24-dien-11-one (2) and (+)-lyoniresinol (3), were isolated from the bark of Elaeocarpus hygrophilus. Their chemical structures were elucidated by spectroscopic NMR, HR-IDA- TOF-MS analysis, and by comparison with the spectral data of corresponding compounds in the literature. Two cucurbitacins (1) and (2) were evaluated for their α-glucosidase inhibitory activity and cytotoxic against KB, MCF-7, Hep G2, and A549 cancer cell lines. For the α-glucosidase inhibitory activity, compound 1 showed an equivalent effect (IC50 197.4 ± 4.1 µM) compared to the acarbose, a positive control (IC50 208.5 ± 4.7 µM). And for the cytotoxicity, 2 was inactive while 1 was slightly sensitive against KB cells (IC50 233.3 ± 2.5 µM).

Preparation, spectroscopic and anticancer investigations of metal-drug complexes associated between flumequine antibiotic drug with lanthanum(III), samarium(III) and terbium(III) chloride

Flumequine ligand (FLQ) metal complexes of the [M(FLQ)2(Cl)(H2O)].nH2O type, where M are (La(III), Sm(III), and Tb(III)) and FLQ is flumequine have been synthesized. The FLQ metal complexes could be prepared using MCl3 : flumequine in stoichiometry of 1:2 in situ bidentate chelation. The characterization of FLQ complexes obtained have been done using elemental analyses (%C, %H and %N), molar conductivity (Ʌm), infrared spectroscopy (FTIR), electronic spectra (UV-Vis), thermal analysis (TGA), and physicochemical techniques such as X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) measurements at room temperature. Accordingly, these complexes are indicative of an octahedral coordination structure. Flumequine ligand has a bidentate fashion through the oxygen atoms of carbonyl (quinolone) and carboxylic groups. The findings demonstrated the anti-cancer efficacy of these compounds against HepG-2 and MCF-7 cancer cell lines at extremely low doses of up to 58.2 mg/mL. The La(III) complex was shown to have the highest selectivity against cancer cells in comparable with both samarium and terbium(III) complexes.
 KEY WORDS: Flumequine, Lanthanide metal ions, FTIR, EDX, Complexation, Anticancer activity
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 671-684. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.10

Dual drug-loaded cubosome nanoparticles for hepatocellular carcinoma: a design of experiment approach for optimization and in vitro evaluation

BackgroundLiver cancer, a formidable and complex disease, poses a significant global health threat, stemming from various causes, including chronic infections like hepatitis B and C, cirrhosis, and lifestyle factors. In liver cancer treatment, targeted delivery revolutionizes precision therapy, minimizing side effects by directing drugs specifically to cancer cells. This study aims to develop and statistically optimize cubosomal formulations containing piperine and quercetin with the goal of augmenting their activity against hepatocellular carcinoma.ResultsEmploying a central-composite design, we utilized Design-Expert® software to guide the experiment. The key formulation variables were the concentration of glyceryl monooleate (GMO) and Poloxamer-407, while the dependent responses were particle size (PS) and entrapment efficiency (EE%). The optimized cubosomal formulation was validated through the utilization of high-resolution transmission electron microscopy (HR-TEM), in vitro release studies, and an in vitro cell proliferation assay conducted on the HepG2 cell line. High-performance liquid chromatography was employed for the determination of piperine and quercetin in the optimized cubosomal nanoparticle. The optimized formulation had a composition of 2.5 (w/w%) GMO and 0.5 (w/w%) Poloxamer 407. The predicted values for PS and EE% were 102.34 and 75.11%, respectively. The cytotoxicity of the optimized cubosomal formulation exhibited enhanced efficacy on the HepG2 cancer cell line, even at lower concentrations, when compared to the standard. Notably, it demonstrated a superior cytotoxic effect on the liver cancer cell line.ConclusionThe findings of the study indicated that cubosomes exhibit promise as an effective carrier for delivering piperine and quercetin, addressing hepatocellular carcinoma effectively.Graphical abstract

Zinc oxide‐cadmium(II) sulfide heterostructure as a potential photocatalyst for preparing substituted chromenes and its anti‐liver cancer activity

There are ongoing studies on the potential use of chromene derivatives in liver cancer therapy. They have shown promising results in preclinical studies for liver cancer, including inhibiting tumor growth and inducing apoptosis. Herein, the nanosized hybrid material zinc oxide (ZnO)–cadmium sulfide (CdS) is prepared using a green and ecofriendly procedure. The nanomaterial was characterized by FE‐SEM, transmission electron microscopy, energy dispersive X‐ray, DRS, X‐ray diffraction, and Fourier transform infrared spectroscopy. The photocatalytic proficiency of ZnO–CdS was then scrutinized in the fabrication of some 4H‐chromenes in a mild condition. The outcomes of this study revealed that the nanophotocatalyst has high photocatalytic reactivity and acceptable reusability in the desired condensation reaction. Furthermore, a preliminary in vitro cellular toxicity assay was performed on ZnO–CdS nanoparticles using HepG2 cancer cell line through MTT assay.

Design and In Silico and In Vitro Evaluations of a Novel Nicotinamide Derivative as a VEGFR-2 Inhibitor

A new nicotinamide derivative, (E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazone)ethyl)phenyl)nicotinamide, was designed as a VEGFR-2 inhibitor. Utilizing the density functional theory (DFT) calculations, the three-dimensional structure of the designed compound was determined, shedding light on its stability and reactivity. Molecular docking revealed its capability to inhibit VEGFR-2, which was further supported by molecular dynamics (MD) simulations confirming its binding to the target protein. In addition, molecular mechanics-generalized born surface area (MM-GBSA), protein-ligand interactions profiler (PLIP), and essential dynamics studies provided further validation of the compound’s precise binding with optimal energy. Then, the “compound 10” was synthesized and subjected to in vitro assays. Compound 10 inhibited VEGFR-2 with an IC50 value of 105.4 ± 0.896 nM, comparing sorafenib’s IC50 value of 61.65 ± 0.934 nM. Besides, it exhibited cytotoxicity against HepG2 and MCF-7 cancer cell lines, with IC50 values of 35.78 ± 0.863 μM and 57.62 μM ± 0.871, comparing sorafenib’s IC50 values of 5.95 ± 0.917 μM and 8.45 ± 0.912 μM. Furthermore, compound 10 demonstrated a lower level of toxicity towards Vero cell lines, with an IC50 value of 127.3 μM. Likewise, compound 10 induced apoptosis in HepG2 cell lines through a flow cytometric analysis in addition to an increase in the levels of caspase-3 and caspase-9. Moreover, compound 10 hindered the migration and healing abilities of HepG2 cells. In conclusion, our study positions compound 10 as a promising candidate for further chemical modifications and biological evaluations.

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC50) values of 2.7–63 μM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC50 of 2.0 and 0.9 μM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC50 = 1.7 μM). Notably, 6c inhibited both kinases, with IC50 values of 2.7 and 3.0 μM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

Investigation of Anticancer Therapy Using pH-Sensitive Carbon Dots-Functionalized Doxorubicin in Cubosomes.

Cancer remains a highly lethal disease due to its elusive early detection, rapid spread, and significant side effects. Nanomedicine has emerged as a promising platform for drug delivery, diagnosis, and treatment monitoring. In particular, carbon dots (CDs), a type of fluorescent nanomaterial, offer excellent fluorescence properties and the ability to carry multiple drugs simultaneously through covalent bonding. In this work, CDs with carbonyl groups on the surface were prepared by aldol condensation and reacted with amine groups in the structure of doxorubicin (DOX) through Schiff base reaction to generate pH-responsive CDs-DOX. On the other hand, cubosomes with three-dimensional lattice structures formed by lipid bilayers have advantageous capabilities of encapsulating various hydrophilic, amphiphilic, and hydrophobic substances. The pH-responsive CDs-DOX are subsequently loaded into cubosomes to form an anticancer therapeutic nanosystem, CDs-DOX@cubosome. Leveraging the unique properties of CDs-DOX and cubosomes, our CDs-DOX@cubosome can enter tumor tissue through the enhanced permeation and retention effect first and conduct membrane fusion with tumor cells to intracellularly release CDs-DOX. Then, the imine bond in CDs-DOX breaks under acidic conditions within human cancer cell lines (HeLa and HepG-2 cells), releasing DOX and achieving enhanced treatment of tumors. Additionally, fluorescent CDs can synchronously achieve real-time in situ diagnosis of tumor tissue. We demonstrate that our CDs-DOX@cubosome works as an excellent drug delivery system with therapeutic efficiency enhancement to the tumor and reduced side effects.