Normal Embryonic Kidney Cell Line Research Articles

Synthesis of Novel Cu(II), Co(II), Fe(II), and Ni(II) Hydrazone Metal Complexes as Potent Anticancer Agents: Spectroscopic, DFT, Molecular Docking, and MD Simulation Studies.

Metal complexes [FeL], [NiL]·H2O, [CuL], and [CoL]·H2O were formed by the ligand (L, 4-fluoro-N'-(2-hydroxybenzylidene)benzohydrazide) reacting with Fe(OAc)2, Ni(OAc)2·4H2O, Cu(OAc)2·H2O, and Co(OAc)2·4H2O. The produced compounds were characterized using a variety of methods, such as NMR, UV-vis, FT-IR, magnetic susceptibility, elemental analysis, and molar conductivity. The spectrum of the data indicates that the geometry of the complex molecular structures is octahedral with six coordination sites. The ligand and its different metal complexes were tested in a human lung cancer cell line and a normal embryonic kidney cell line. A cytotoxic assay revealed that L-Cu is the most potent chelate against cancer cell lines. A computational study was performed to rationalize this finding. The binding potential of relatively active compounds to a suitable target was analyzed. For this purpose, a target that is known to be inhibited by small compounds with a scaffold similar to that of the synthesized compounds, lysine-specific demethylase 1 (LSD1), was first determined. Molecular docking studies demonstrated that L-Cu has a high binding potential to LSD1 at a level comparable to that of a standard ligand. Molecular dynamics (MD) simulations revealed that L-Cu and L form stable complexes with the enzyme. Furthermore, the MD simulation study showed that L-Cu remained inside the binding pocket of the enzyme during the 200 ns simulation period. Density functional theory (DFT) studies demonstrated that the chemical stability of L was higher than that of its chelate form, L-Cu.

Microwave-assisted synthesis, spectral characterization, and biological activities of complexes of a Schiff base derived from S-benzyl dithiocarbazate

Co(II), Ni(II), Zn(II), and Cd(II) complexes were synthesized from a Schiff base ligand, benzyl-2-(1-(thiophen-2-yl)propylidene)hydrazine-1-carbodithioate (BTPHC), by conventional as well as microwave irradiation methods. The ligand and its metal complexes were characterized by spectroscopic techniques (FT-IR, UV-vis, mass spectrometry, and 1H NMR) and powder X-ray diffraction. Based on magnetic measurements and spectral data, octahedral environments for Co(II) and Ni(II) complexes and tetrahedral environments for Zn(II) and Cd(II) complexes are proposed. The metal(II) complexes were active toward bacterial and fungal strains. Antidiabetic studies showed that the Cd(II) complex possesses greater potential as an antidiabetic agent than the other metal complexes and the ligand. Antioxidant studies indicate that the Zn(II) and Cd(II) complexes possess high radical scavenging activities. The synthesized ligand and metal(II) complexes were screened for their anticancer properties against two human cancer cell lines MCF-7 and HeLa using an MTT cell viability assay. The Ni(II) complex excelled in halting the proliferation of HeLa and MCF-7 cancer cell lines with IC50 values of 46.63 µM and 80.90 µM, respectively, whereas it displayed insignificant cytotoxicity against the human normal embryonic kidney cell line (HEK293) with IC50 = 300.41 µM.

Facile synthesis and characterization of W-doped TiO2 nanoparticles: Promising ancticancer activity with high selectivity

In this research work, the effect of tungsten (W) doping on the crystal structure, morphology and anticancer activity of titanium dioxide (TiO2) nanoparticles were studied. The synthesized W doped TiO2 nanoparticles have been characterized by spectroscopic and microscopic techniques. XRD pattern of pure TiO2 and 1 wt% W-doped TiO2 nanoparticles confirms the anatase structure and increase in the W-doping changes the phase of TiO2 to rutile. The images of HRTEM clearly confirm that size of 5 wt% W-doped TiO2 nanoparticles are in the range of ~ 40 nm. The FESEM images show the agglomerated spherical-like morphology for pure TiO2, 1 wt%, 3 wt% W-doped TiO2 nanoparticles and flower like morphology for 5 wt% W-doped TiO2 nanoparticles. Both pure TiO2 and W-doped TiO2 nanoparticles did not show any notable cytotoxicity against human normal embryonic kidney cell line (HEK 293), but showed effective cytotoxicity against HeLa cancer cell lines evaluated by MTT assay.

Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway.

Wogonin, an active component derived from Scutellaria baicalensis, has shown anti-tumor activities in several malignancies. However, the roles of wogonin in RCC cells remain elusive. Here, we explored the effects of wogonin on RCC cells and the underlying mechanisms. We found that wogonin showed significant cytotoxic effects against RCC cell lines 786-O and OS-RC-2, with much lower cytotoxic effects on human normal embryonic kidney cell line HEK-293 cells. Wogonin treatment dramatically inhibited the proliferation, migration, and invasion of RCC cells. We further showed that by inhibiting CDK4-RB pathway, wogonin transcriptionally down-regulated CDC6, disturbed DNA replication, induced DNA damage and apoptosis in RCC cells. Moreover, we found that the levels of p-RB, CDK4, and Cyclin D1 were up-regulated in sunitinib resistant 786-O, OS-RC-2, and TK-10 cells, and inhibition of CDK4 by palbociclib or wogonin effectively reversed the sunitinib resistance, indicating that the hyperactivation of CDK4-RB pathway may at least partially contribute to the resistance of RCC to sunitinib. Together, our findings demonstrate that wogonin could induce apoptosis and reverse sunitinib resistance of RCC cells via inhibiting CDK4-RB pathway, thus suggesting a potential therapeutic implication in the future management of RCC patients.

Design, Synthesis, and Targeted Delivery of Fluorescent 1,2,4-Triazole-Peptide Conjugates to Pediatric Brain Tumor Cells.

Most of the chemotherapeutics and drug-delivery models pose serious health problems and several undesirable side effects due to nonspecificity, lack of proper targeting system, and their large sizes. The rational design and synthesis of target-specific chemotherapeutics are highly important. This research work is focused on the rational design, synthesis, and anticancer studies of fluorescent 1,2,4-triazole–peptide conjugates for the development of target-specific anticancer drugs. Three novel 1,2,4-triazole derivatives: 4-(4-fluorobenzylidenamino)-3-hydrazino-5-mercapto-1,2,4-triazole (4FBAHMT, 2a), 4-(3,4,5-trimethoxybenzylidenamino)-3-hydrazino-5-mercapto-1,2,4-triazole (TMOBAHMT, 2b), and 4-(4-benzyloxy-2-methyloxbenzylidenamino)-3-hydrazino-5-mercapto-1,2,4-triazole (4BO2MOBAHMT, 2c) were synthesized after screening through molecular docking procedures. The docking studies were performed between ligand molecules and αvβ6 integrin protein. Fluorescent carbon nanoparticles (CNPs, 3) were conjugated with 1,2,4-triazole derivatives (2a–c) and l-carnosine (LC) dipeptide to get their corresponding conjugates (4a–c). The title double conjugates were characterized by spectroscopic (UV/vis spectroscopy, fluorescence spectroscopy, and FTIR spectroscopy) and microscopic (scanning electron microscopy, transmission electron microscopy, and atomic force microscopy) techniques. In vitro efficacy of fluorescent 1,2,4-triazole–peptide conjugates was investigated against two pediatric brain tumor cell lines (CHLA-200 & SJGBM2) and human embryonic kidney cell line (HEK293 as a control) by employing cell proliferation assay/MTS assay and fluorescence microscopy. 1,2,4-Triazole derivatives and their conjugates showed potent and selective anticancer activity against CHLA-200 and SJGBM2 cell lines. Cell proliferation assay and fluorescence microscopy results revealed that conjugates were more highly selective and cytotoxic than control drug temozolomide (TM) against both cell lines. CNPs are highly biocompatible and the quantum-sized conjugates were nontoxic for normal embryonic kidney cell line (HEK 293). The experimental results of MTS bioactivity assay and fluorescence microscopy were in close agreement with the theoretical results of molecular docking studies.

Anti-proliferative activity, molecular modeling studies and interaction with calf thymus DNA of novel ciprofloxacin analogues

In our pursuit to expand new potential anticancer leads, a series of eighteen novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized and evaluated anti-proliferative activity against five human cancer cell lines such as A549 (lung cancer), Mia Paca (pancreatic cancer), HeLa (cervical cancer), MDA MB-231 (breast cancer), MCF-7 (breast cancer) and normal embryonic kidney cell line (HEK) were carried out using MTT assay. Few of the synthesized analogues exhibited potent anticancer activity against the cancer cell lines at a lower concentration. The synthesized compounds showed the less toxic effect on normal human embryonic kidney cell line (HEK) compared with doxorubicin. Noticeably, compound 3o exhibited potent activity against all five cancer cell lines compared with ciprofloxacin. Further study exposed that compound 3o could competently intercalate into calf thymus DNA to form 3o-DNA complex which might block DNA replication to apply anti-proliferative activity. Docking simulation studies supported by molecular interactions with DNA type II topoisomerase. These derivates can become lead structures for the development of potential anticancer drugs. Eighteen CP analogues were synthesized and evaluated for anti-proliferative activity. The interactions with DNA topoisomerase II were supported by molecular docking studies. 3o showed promising anticancer activity than CP against MCF7 cell line and interaction with calf thymus DNA was studied by fluorescence spectroscopy.

Silica‐Coated Metal Oxide Nanoparticles: Magnetic and Cytotoxicity Studies

AbstractMetal oxide nanoparticles are one of the most important categories of nanomaterials. Increasing use of metal oxide nanoparticles necessitates an improved understanding of their potential impact on human health. We demonstrated that silica(SiO2) coated magnetic transitional metal oxides (α‐Fe2O3, NiO, Co3O4) nanoparticles were facilely synthesized through wet chemical methods. Structural, morphological and compositional details of these nanoparticles have been investigated. Optical absorption study was also carried out to compare the bare and silica coated metal oxide nanoparticles. Magnetic measurement of these three silica coated metal oxide samples reveals their ferromagnetic behavior. The biocompatibility of nanoparticles is the prerequisite for their applications in biomedicine, but can be misleading due to toxicity of these nanomaterials. Cytotoxicity was evaluated for these materials via Cell culture, MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐tetrazolium bromide) assay in human normal embryonic kidney cell line (HEK‐293) and human breast adenocarcinoma cell line (MCF‐7) which shows its non‐toxicity towards HEK‐293 and the effectiveness of the sample towards the destruction of MCF‐7. Measurements of nanoparticles treated cells by morphological assessment assay demonstrate that these nanomaterials exhibit excellent cellular viability. Thus, silica coated magnetic metal oxide nanomaterials appear to be a new roadmap in the search of biocompatible resources for medical applications.

The cytotoxic, apoptotic and oxidative effects of carbonic anhydrase IX inhibitor on colorectal cancer cells.

Colorectal cancer (CRC) is the third most common tumor, malignant and has developed one of the main reasons of cancer mortality. According to studies conducted recently; carbonic anhydrase 9 (CAIX) is an especially attractive target for cancer therapy, in part since it is limited way expressed in normal tissues on the other hand in a wide variety of solid neoplasia are overexpressed. The aim of this study was to appreciate the effects of CAIX inhibitor, namely novel synthesized sulfonamide derivative (H-4i) with high affinity for CAIX, in CAIX-positive human colorectal cancer cell (HT-29) and CAIX-negative human normal embryonic kidney cell line (HEK-293). For this reason, we planned to investigate apoptotic, cytotoxic and oxidative stress activity of H-4i on HT-29 and HEK-293 cell lines. Cell viability determined by WST-1 assay afterwards IC50 values, apoptosis and cell cycle induction measured by flow cytometric analysis, intracellular free radical induction performed by reactive oxygen species (ROS) analyses. The IC50 value of the sulfonamide derivative compound was found to be very low, especially in HT-29 cells, when compared to human normal cells. This research found that H-4i significantly increased cytotoxicity and ROS production, caused significant signs of apoptosis level. High level of ROS and apoptosis lead to arrest the cell cycle and reduce cell survival. The most obvious finding to emerge from the analysis that novel synthesized sulfonamide derivative H-4i is effective on HT-29 more than HEK-293. Therefore, novel derivative H-4i might be used as an anti-cancer potential compound on CRC.

Fluorinated pyrrole incorporated 2-thiazolyl hydrazone motifs: a new class of antimicrobial and anti tuberculosis agents.

In aim of obtaining novel bio-active compounds, a new series of fluorinated 1-(4-(aryl)thiazol-2-yl)-2-((1-(aryl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)hydrazines (5a-t) and 1-(4-(4-aryl)thiazol-2-yl)-2-((3-(2,4-dichlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazines (8a-d) were synthesized and screened for their antibacterial and antifungal activities. The potent compounds were further screened in vitro for anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Compounds 5a, 5c-5h and 5m were found to be good inhibitors of B. subtilis with MIC ranging from 0.2 to 0.8µgmL-1, which are nearly three to ten times more potent than the standard drug Ciprofloxacin. Compounds 5a, 5h-5k and 5o exhibited potent antifungal activity against C. albicans strain with MIC ranging from 0.4 to 1.6µgmL-1. Compounds 8a-8c were found to be excellent inhibitors of A. niger. Compounds 5a and 5k showed significant anti tubercular activity with MIC 3.12 and 6.25µgmL-1 respectively. Furthermore, highly active compounds were tested for their preliminary toxicity profile by hemolytic assay and were found to be non hemolytic at higher concentration with good selectivity index. Cytotoxicity of the potent compounds 5a, 5d, 5g, 5i and 5k was checked by MTT assay using normal embryonic kidney cell line HEK 293 and found to be non-toxic up to 50-200 times the MIC for antibacterial activity.

Biological screening of novel derivatives of valproic acid for anticancer and antiangiogenic properties.

Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between 2-20 μM in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

MicroRNA differential expression profile in nephroblastoma cell line versus normal embryonic kidney cell line

To explore the microRNA (miRNA) differential expression profile between nephroblastoma cell line G401 and normal embryonic kidney cell line CCC-HEK-1 so as to provide rationales for the role of miRNA in the pathogenesis of nephroblastoma. Three samples from G401 cell line and another 3 samples from CCC-HEK-1 cell line were chosen as the experimental group and the control group respectively. miRNA profiles in these samples were analyzed by microarray. The threshold value used to screen up and down-regulated miRNAs was fold change ≥ 2 or ≤ 50.0%. And real-time PCR was used to validate the reliability of microarray. Seventy-one miRNAs were found up-regulated in the experimental group and 11 of them were more than 8 times versus control group. In addition, 59 miRNAs were found down-regulated and 11 of them were 12.5% versus control group. Overall, there were significant differences in the expression of miRNA between G401 and CCC-HEK-1 cell lines. There is a differential expression of miRNA between G401 and CCC-HEK-1 cell lines. It may be related with occurrence and metastasis of nephroblastoma.