Human Cervix Adenocarcinoma Research Articles

Synthesis of Aryl‐Functionalized Benzo[d,e]Benzo[4,5]İmidazo[2,1‐a]Isoquinolin‐7‐One Derivatives: DNA Intercalation Causing Cytotoxicity

AbstractThis study focuses on the cytotoxic effect properties of 4‐aryl‐functionalized benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one (4‐X−Ar−BBI). The electron‐withdrawing and electron‐donating substituents located at the para position of the phenyl ring attached to the heterocyclic structure have altered the pi electron density within the structure. This change in electron density has influenced the intercalation ability of the heterocyclic structure and has impacted the intensity of its interaction with DNA. The 4‐aryl‐benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one derivatives (4‐X−Ar−BBI) were prepared via the Suzuki–Miyaura cross‐coupling reaction. The optimum reaction conditions were determined to be 70 °C for 5 hours using catalyst 1 and K2CO3, resulting in a yield of 96 % of 4‐H−Ar−BBI. Characterization of all compounds (4‐X−Ar−BBI) was performed using Fourier Transform Infrared spectroscopy, mass spectrometry, and 1H‐ and 19F‐NMR spectroscopies. The cytotoxic activities of the compounds (4‐X−Ar−BBI) were investigated against cancer cell lines, specifically HeLa (human cervix adenocarcinoma epithelial), PC3 (human prostate), and MCF‐7 (human breast). The stability of 4‐CN−Ar−BBI and the binding modes between 4‐CN−Ar−BBI and DNA were investigated via 1H‐NMR spectroscopy and UV‐Vis spectroscopy, respectively. 4‐CH3−3‐NO2−Ar−BBI exhibited the most potent cytotoxic activity against MCF‐7, and 4‐F−Ar−BBI showed the highest activity against HeLa, with IC50 values of 3.675 and 7.370 μM, respectively.

Chemical composition, antioxidant, antimicrobial and anti-proliferative activities of the leaf essential oil of Melaleuca polandii grown in the coastal plains of eastern India

Melaleuca polandii, commonly known as “Gold-tipped Bottlebrush”, is widely grown in Indian gardens and parks as an ornamental plant. In the present study, the chemical composition, antioxidant, antimicrobial and cytotoxic activities of M. polandii leaf essential oil (MPLEO) have been investigated. GC-MS analysis of MPLEO isolated from plants grown along the coastal plains of Eastern India revealed the presence of 50 constituents with α-pinene (46.17%), 3Z-hexenyl acetate (10.10 %), α-terpineol (5.43%), limonene (3.63%) and ρ-cymene (2.44 %) as the major constituents. MPLEO exhibited moderate antioxidant capacity in DPPH, ABTS and Reducing ability assays with IC50 values of 7.94 ± 0.34 μg/mL, 5.71 ± 0.21 μg/mL and EC50 7.09 ± 0.35 μg/mL, respectively. Of the 5 bacterial strains tested, the EO exhibited highest sensitivity against Bacillus subtilis with the ZOI of 12.66 ± 0.57 mm and strong antimicrobial activity against Staphylococcus saprophyticus with MIC value of 6.25 μg/mL. MPLEO exhibited significant cytotoxic effects against Human alveolar lung adenocarcinoma (A549), Human hepato-cellular carcinoma (HepG2), Human cervix adenocarcinoma (HeLa) and normal Human Embryonic Kidney cell (HEK-293) as evaluated through MTT assay with IC50 values of 9.5 ± 0.38 μg/mL, 22.73 ± 0.95 μg/mL, 20.41 ± 0.82 μg/mL and 237.68 ± 9.26 μg/mL, respectively. The findings of the present study demonstrated that MPLEO could be considered as a potential bioresource having applications in pharmaceutical industries as an antibacterial and antiproliferative agent.

In vitro anticancer studies of a small library of cyclic lipopeptides against the human cervix adenocarcinoma HeLa cells

Various cyclic lipopeptides (CLPs, 23 compounds) were tested for their antitumor potential against human cervix adenocarcinoma HeLa cells. From the fast screening (tested concentrations: 0.01 and 10 ?M) compound 10 ((12S,6S,10S,13S)-6-((R)-sec-butyl)-7-(2-(dodecylamino)-2-oxoethyl)-13-isopro-pyl-82-nitro-2,5,12,15-tetraoxo-4,7,11,14-tetraaza-1(1,2)-pyrrolidina-8(1,4)-benz-enacyclopentadecaphane-10-carboxamide) was identified as active against HeLa cell line. The MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and CV (crystal violet) assays revealed at least five times higher cyto-toxic potential of 10 (IC50 = 12.3?1.8 ?M, MTT; 9.4?1.5 ?M; CV) in compar-ison to control drug natural occurring CLP surfactin (IC50 = 64.9?0.8 ?M, MTT; 76.2?1.6 ?M; CV). The cell cycle analysis performed by DAPI (4',6-di-amidino-2-phenylindole) assay indicated the involvement of apoptosis in HeLa cell death upon treatment with 10, which was confirmed by apoptosis assay (annexin V/PI). Furthermore, during this process caspase activation could be detected (ApoStat assay, immunocytochemistry caspase-3 analysis). The flow cytometry analysis did not display induction of autophagy as a possible death mechanism in HeLa cells upon 10 treatment. The current findings could be used to design more effective CLPs based on 10 structure as potential anticancer agents.

Bidesmosidic and monodesmosidic triterpenoid saponins from the grain of Amaranthus hypochondriacus

Five known bidesmosidic triterpenoid saponins (1–5) and their hydrolysates, namely two new monodesmosidic triterpenoid saponins (1′ and 2′) and three known saponins (3′–5′), were isolated from Amaranthus hypochondriacus seeds. The structures of the new compounds were determined using interpreting 1D and 2D nuclear magnetic resonance (NMR) data and high-resolution electrospray ionisation mass spectrometry (HRESI-MS) analyses as 3-O-β-D-glucuronopyranosyl-30-normedicagenic acid (1′) and 3-O-[α-L-rhamnopyranosyl (1 → 3)-β-D-glucuronopyranosyl] bayogenin (2′). For the first time, 5 and 5′ were isolated from Medicago plants as the first examples of glycosides in medicagenic acid from Amaranthus plants. While bidesmosidic saponins showed no cytotoxicity, monodesmosidic saponins, except for 1′, showed moderate cytotoxicity against human cervix adenocarcinoma (HeLa) cells. In addition, monodesmosidic saponins showed anti-fungal activity against the rice blast fungus (Pyricularia oryzae).

Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models.

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical cancer (CC-5). The effect of avarol on cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa cancer cells (10.22 ± 0.28 μg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new anticancer medicine.

Design, synthesis, and biological evaluation of diarylpyrazole derivatives as antitumor agents targeting microtubules

A new series of novel diarylpyrazole derivatives as microtubule destabilizers were synthesized and evaluated for the anti-proliferative activities. Anti-proliferative assays were performed on the human cervix adenocarcinoma cell line (HeLa) and human gastric adenocarcinoma cell line (SGC-7901), and the compound 9s containing indole ring showed great anti-proliferative activity against HeLa cells with IC 50 value of 1.9 ± 0.11 μM. Further biological studies showed that 9s was able to inhibit tubulin polymerization, disrupt the cytoskeleton, block the cell cycle in the G2/M phase, and induce cell apoptosis in a concentration-dependent manner. In addition, the results of molecular docking studies showed that compound 9s could bind tightly to the colchicine binding site of tubulin through hydrogen bonding interaction. These preliminary results recommend that compound 9s is likely to be a microtubule destabilizer that deserves further investigation.

Implication of phenol red in quantification of cultured cancerous cells using near-infrared spectroscopy and aquaphotomics

This study aims to evaluate the ability of absorbance spectra in the near-infrared (NIR) region to predict the number of cells for different cell lines. The cancerous cell lines were human cervix adenocarcinoma (HeLa) and human prostate carcinoma (DU145), and L929 was a normal mouse skin fibroblast. The number of cells varied from 50,000 to 275,000 with an interval of 25,000 for each cell line. Vis-NIR absorbance spectra (400–1100 nm) at each number of cells (50,000–275,000) for L929, DU145, and HeLa cell lines cultured in media with and without phenol red were recorded. Multiple linear regression (MLR) and partial least squares regression (PLSR) models were developed in the NIR region (680–1050 nm) to quantify the number of cells for the three cell lines. The outcomes showed that the quantification analysis of the number of cells using MLR and PLSR models produced high prediction accuracy with R2≥ 93%. The best results were obtained using PLSR for the preprocessed spectra using an orthogonal signal correction method. It was found that the presence of phenol red in the culture medium improved the prediction accuracy in the case of HeLa (SECV = 271 cells) and DU145 (SECV = 250 cells) cell lines, but the accuracy was higher when phenol red was not present for the L929 cell line (SECV = 24 cells). In addition, the existence of phenol red boosted the accuracy when the global PLSR model was built, irrespective of the cell type (SECV = 7,754 cells). The effect of phenol red was explained in the terms of its impact on the water molecular structure of the cells’ culture medium which influences the light scattering.

Integration of near-infrared spectroscopy and aquaphotomics for discrimination of cultured cancerous cells using phenol red

Presently, mammalian cell lines are the most utilized hosts for the production of biopharmaceuticals. Optical spectroscopy is extensively used for the physical or physiological measurements of cellular features to study the diagnosis, prognosis, and treatment of different cancers. Near-infrared (NIR) spectroscopy and aquaphotomics are ubiquitous techniques increasingly used for nondestructive assessment. The key objective of this study is to evaluate the feasibility of absorbance spectra in the NIR region (700–1100 ​nm) coupled with aquaphotomics analysis to classify the different cancerous cell lines. Human cervix adenocarcinoma cells (HeLa) and human prostate carcinoma (DU145) were the cancerous cell lines, while normal mouse skin fibroblast (L929 ​cell line) was used as a reference for the assessment. The NIR absorbance spectra for 50 ​000 to 275 ​000 ​cells of L929, DU145, and HeLa cell lines in culture media prepared with and without phenol red (PhR) were subjected to principal component analysis (PCA) and soft independent modeling of class analogies (SIMCA) models. The PCA of the spectral absorbance data revealed a clear discrimination between the three cell lines, with subgroups detected based on the presence or absence of PhR in the culture medium. The SIMCA method showed a high accuracy of classification, where larger class distances were obtained among the non-stained cells.

Antiproliferative and cytotoxic effects of bioactive compounds isolated from Onosma bourgaei.

Onosma species have been used commonly for traditional medicine for years due to their bioactive compounds content. Onosma bourgaei aerial part was extracted with hexane and methanol successively. The methanol extract was subjected to chromatographic techniques to isolate allantoin (1), 3,4-dihydroxybenzaldehyde (2), luteolin-7-O-glucoside (3), apigenin-7-O-β-glucoside (4), diosmetin-7-O-β-glucoside (5), rosmarinic acid (6), and globoidnan A (7). The structure of isolated compounds were identified by spectroscopic techniques such as 1D-NMR, 2D-NMR, FTIR, and LC-TOF/MS/MS. Antiproliferative activity of extract and natural compounds were carried out using HeLa (human epithelial cervix adenocarcinoma, ATCC® CCL-2™), HT29 (human colorectal adenocarcinoma, ATCC® HTB38™), MCF7 (human mammary gland adenocarcinoma, ATCC® HTB22™), and A549 (human lung carcinoma, ATCC® CCL185™) cancerous cells and normal cells, FL (human epithelial amnion cell, ATCC® CCL62™). Lactate dehydrogenase (LDH) was performed for cytotoxicity. The compounds, 4, 6, and 7 displayed the strong antiproliferative activity against corresponding cell lines. Apigenin-7-O-β-glucoside (4) revealed the excellent activity on HeLa, HT29, A549, and MCF6 cancer cell lines with the values of (IC50, µM) 167.3, 196.8 181.1, and 203.5, respectively, compared standard compound, cisplatin.

Folic Acid and Chitosan-Functionalized Gold Nanorods and Triangular Silver Nanoplates for the Delivery of Anticancer Agents.

BackgroundAdvances in the field of nanotechnology have shed light on the applications of nanoparticles for cancer treatment.MethodsFolic acid and chitosan-functionalized gold nanorods (FACS-R) and triangular silver nanoplates (FACS-T) were synthesized and their properties were elucidated by UV-visible spectrophotometry, Fourier-transform infrared spectroscopy, field emission transmission electron microscopy and high-resolution X-ray diffraction.ResultsThe average size of the FACS-R was determined to be a transverse length of 13.1 ± 1.8 nm and a longitudinal length of 47.2 ± 8.9 nm with an aspect ratio of 3.6. The average size of FACS-T was measured to be 31.8 ± 7.7 nm. Colloidal solutions of FACS-R and FACS-T were stable on the shelf at ambient temperature for 14 days in the dark. Anticancer agents were encapsulated in FACS-R and FACS-T. FACS-T showed a higher encapsulation efficiency with docetaxel, paclitaxel and diallyl disulfide than FACS-R. The cell viability on human gastric adenocarcinoma cells (AGS), human epithelial cervix adenocarcinoma cells (HeLa) and human colorectal adenocarcinoma cells (HT-29) after treatment with anticancer agent-encapsulated FACS-R and FACS-T was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Interestingly, paclitaxel-encapsulated FACS-R and FACS-T showed the highest percentages of early and late apoptosis on HeLa cells. A cell cycle analysis demonstrated increased G2/M arrest on HeLa cells with docetaxel and paclitaxel-encapsulated FACS-R and FACS-T. The FACS-T induced more G2/M arrest on HeLa cells than the FACS-R. To assess applications in near-infrared photothermal therapy (PTT), the cell viability on HeLa cells with the anticancer agent-encapsulated FACS-R and FACS-T was assessed in the presence or absence of 808 nm laser irradiation. The results showed that 808 nm laser irradiation significantly decreased cell viability.ConclusionCollectively, the triangular silver nanoplates were more effective than the gold nanorods for PTT. We believe that as-prepared nanoparticles have remarkable features and will become promising future nanomedicine.

Transcriptomics Reveals the Mevalonate and Cholesterol Pathways Blocking as Part of the Bacterial Cyclodipeptides Cytotoxic Effects in HeLa Cells of Human Cervix Adenocarcinoma

The incidence of human cervix adenocarcinoma (CC) caused by papillomavirus genome integration into the host chromosome is the third most common cancer among women. Bacterial cyclodipeptides (CDPs) exert cytotoxic effects in human cervical cancer HeLa cells, primarily by blocking the PI3K/Akt/mTOR pathway, but downstream responses comprising gene expression remain unstudied. Seeking to understand the cytotoxic and anti-proliferative effects of CDPs in HeLa cells, a global RNA-Seq analysis was performed. This strategy permitted the identification of 151 differentially expressed genes (DEGs), which were either up- or down-regulated in response to CDPs exposure. Database analysis, including Gene Ontology (COG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed differential gene expression on cancer transduction signals, and metabolic pathways, for which, expression profiles were modified by the CDPs exposure. Bioinformatics confirmed the impact of CDPs in the differential expression of genes from signal transduction pathways such as PI3K-Akt, mTOR, FoxO, Wnt, MAPK, P53, TGF-β, Notch, apoptosis, EMT, and CSC. Additionally, the CDPs exposure modified the expression of cancer-related transcription factors involved in the regulation of processes such as epigenetics, DNA splicing, and damage response. Interestingly, transcriptomic analysis revealed the participation of genes of the mevalonate and cholesterol biosynthesis pathways; in agreement with this observation, total cholesterol diminished, confirming the blockage of the cholesterol synthesis by the exposure of HeLa cells to CDPs. Interestingly, the expression of some genes of the mevalonate and cholesterol synthesis such as HMGS1, HMGCR, IDI1, SQLE, MSMO1, SREBF1, and SOAT1 was up-regulated by CDPs exposure. Accordingly, metabolites of the mevalonate pathway were accumulated in cultures treated with CDPs. This finding further suggests that the metabolism of cholesterol is crucial for the occurrence of CC, and the blockade of the sterol synthesis as an anti-proliferative mechanism of the bacterial CDPs, represents a reasonable chemotherapeutic drug target to explore. Our transcriptomic study supports the anti-neoplastic effects of bacterial CDPs in HeLa cells shown previously, providing new insights into the transduction signals, transcription factors and metabolic pathways, such as mevalonate and cholesterol that are impacted by the CDPs and highlights its potential as anti-neoplastic drugs.

Synthesis and investigation of antiproliferative activity of Ru-NHC complexes against C6 and HeLa cancer cells.

The 2-methylpyridine, 2-diethylaminoethyl, and isopentyl linked a series of symmetric and unsymmetric benzimidazolium salts 2a-e were prepared and used in the synthesis of silver-N-heterocyclic carbene (NHC) complexes (3a-e). The Ru(II)-NHC complexes (4a-h) were synthesized via transmetalation reaction from 3a-e. 4a-h complexes were converted to Ru(II)-NHC.HCl complexes (5ah) by HCl solution of diethyl ether and characterized by different spectroscopic techniques such as 1H and 13C NMR, LC/MS-Q-TOF, FT-IR, elemental analysis, and melting point detection. We examined the effect of the structural difference of complexes on anticancer activity via different arenes and metal centers. Antiproliferative activity of 5a-h and 3a was tested against human cervix adenocarcinoma (HeLa) and rat glioblastoma (C6) cell lines by ELISA assay. The IC50 value of 5b, 5c and 5e complexes exhibited good cytotoxic activity than cisplatin on C6 (14.2 ± 0.5 mM; 16.2 ± 0.4 mM; 24.2 ± 0.7 mM, respectively) and HeLa (11.1 ± 0.5 mM; 13.7 ± 0.3 mM; 22.8 ± 0.8 mM, respectively) cell lines.

New copper(II) cyclam complexes with aminocarboxylate co-ligands: Synthesis, characterization, and in vitro antiproliferative and antibacterial studies

Two new cationic Cu(II) complexes of cyclam (1,4,8,11-tetraazacyclotetradecane) and aminocarboxylate coligands glycine or alanine have been synthesized. The complexes were characterized by elemental analysis (C, H and N), molar electrical conductivity, magnetic susceptibility measurement at room temperature, spectral methods (UV/Vis and Fourier transform infrared), as well as by thermogravimetric (TG) and differential thermal analysis (DTA). The analytical data of the complexes show the formation of mononuclear complexes with general formula [Cu(L)cyc](ClO4)2?nH2O, A) L = glycine, n = 1.5 and B) L = alanine, n = 2.5. The tetradentate ligand cyclam was coordinated to metals through four N donors. The spectroscopic data suggested that the amino carboxylate ligands coordinated via their carboxylate ion moieties. The six- -coordinate octahedral geometry around Cu(II) in both complexes was presumed. TG-DTA analysis indicated that complex B decomposed exothermally in a single step in the range of 310?400?C. The cytotoxic activity of Cu(II) complexes and the starting ligands were tested against human cervix adenocarcinoma cell line (HeLa), human melanoma (FemX) and human colon carcinoma (LS174). The IC50 values for the Cu(II) complexes were from 48.35?82.25 ?M. Both complexes were tested for their antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and the yeast Candida albicans.

Albumin nanoparticles for use in cancer drug delivery

The side effects of chemotherapeutic drugs on healthy organs, as well as cancer cells, are one of the main reasons for the high mortality rates of cancer patients. Controlled drug release studies with biocompatible nanoparticles are becoming increasingly important to prevent drawbacks of traditional chemotherapy treatment. In this study, it is aimed to entrap doxorubicin (DOX) into albumin nanoparticles with a high loading capacity to obtain a long-term release profile. Albumin nanoparticles were prepared through the desolvation method and characterized by transmission electron microscopy. The prepared particles were spherical in shape, having a size between 25 and 100 nm, and the entrapment efficiency was about 87%. The in vitro release profile of DOX-loaded albumin nanoparticles exhibited controlled release of the drug up to 124 days (90.37%). The results showed that DOX was efficiently entrapped into the prepared albumin nanoparticles and the drug was released from the carrier in a controlled manner. Assessment of the cytotoxicity of the obtained nanoparticles on human A549 (human lung adenocarcinoma) and HeLa (human cervix adenocarcinoma) cell lines was carried out through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer cell line cytotoxicity results, consistent with the controlled release profile, evidently showed that DOX-loaded albumin nanoparticles can be a good option in the treatment of cancer.

Antiplasmodial and Cytotoxic Flavonoids from Pappea capensis (Eckl. & Zeyh.) Leaves.

Ethnobotanical surveys indicate that the Masai and Kikuyu in Kenya, the Venda in South Africa, and the Gumuz people of Ethiopia use Pappea capensis for the treatment of malaria. The present study aimed to investigate the phytochemical and antiplasmodial properties of the plant leaves. The bioactive compounds were isolated using chromatographic techniques. The structures were established using NMR, HRMS, and UV spectroscopy. Antiplasmodial activity of P. capensis leaf extract and isolated compounds against chloroquine-sensitive 3D7 P. falciparum was evaluated using the parasite lactate dehydrogenase assay. Cytotoxicity against HeLa (human cervix adenocarcinoma) cells was determined using the resazurin assay. The extract inhibited the viability of Plasmodium falciparum by more than 80% at 50 µg/mL, but it was also cytotoxic against HeLa cells at the same concentration. Chromatographic purification of the extract led to the isolation of four flavonoid glycosides and epicatechin. The compounds displayed a similar activity pattern with the extract against P. falciparum and HeLa cells. The results from this study suggest that the widespread use of P. capensis in traditional medicine for the treatment of malaria might have some merits. However, more selectivity studies are needed to determine whether the leaf extract is cytotoxic against noncancerous cells.

Binuclear Co(II) complexes with macrocycle and carboxylato ligands: structure, cytotoxicity and thermal behavior

In vitro cytotoxic evaluation, formation constants and thermal stability of four mixed-ligand Co(II) complexes with tpmc = N,N',N",N'"-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane and carboxylate/dicarboxylate co-ligands of formulas [Co2(benz)2tpmc](ClO4)2•3H2O (1), benz– = benzoate anion; [Co2(L)tpmc](ClO4)2•nH2O, L = pht2– (phthalate dianion), n=2 (2), L = ipht2– (isophthalate dianion), n=4 (3) and L = tpht2–(terephthalate dianion), n=4 (4) are reported. The stoichiometric composition of the compounds in the solution were determined spectrophotometrically using Job's methods. Formation constants, K and Gibbs free energy, ΔG values were calculated. The thermal behavior of the complexes was investigated by simultaneous TG/DSC and TG – MS measurements. The cytotoxic effect of the complexes, the free ligands, the DMSO solvent and cis-platin, as referent cytostatic drug, was evaluated on Human cervix adenocarcinoma (HeLa), human melanoma (Fem-x) and human colon carcinoma (LS174) cell lines. The IC50 values were between 12.7–42.3 μM. The first crystal structure determination of the Co(II) complex [Co2(µ-pht)tpmc](ClO4)2•H2O with boat conformation of tpmc ligand, was also done. The complex crystallizes in monoclinic crystal system, C2/c space group. The geometries around both Co(II) atoms are highly distorted octahedral. The Co(II) ions exhibit CoN4O2 coordination environments with the four nitrogen donor atoms of the tpmc ligand and two oxygen atoms belonging to the one carboxylate group of pht2− ligand. The carboxylate groups of pht2− are coordinated in an endo-bidentate mode. The tpmc ligand adopted a boat conformation in which the two coordinated Co(II) atoms are located on the same side of the ring, with Co•••Co distance amounting 5.4799(5) Å.

Fabrication of Tunable 3D Cellular Structures in High Volume Using Magnetic Levitation Guided Assembly.

Tunable and reproducible size with high circularity is an important limitation to obtain three-dimensional (3D) cellular structures and spheroids in scaffold free tissue engineering approaches. Here, we present a facile methodology based on magnetic levitation (MagLev) to fabricate 3D cellular structures rapidly and easily in high-volume and low magnetic field. In this study, 3D cellular structures were fabricated using magnetic levitation directed assembly where cells are suspended and self-assembled by contactless magnetic manipulation in the presence of a paramagnetic agent. The effect of cell seeding density, culture time, and paramagnetic agent concentration on the formation of 3D cellular structures was evaluated for NIH/3T3 mouse fibroblast cells. In addition, magnetic levitation guided cellular assembly and 3D tumor spheroid formation was examined for five different cancer cell lines: MCF7 (human epithelial breast adenocarcinoma), MDA-MB-231 (human epithelial breast adenocarcinoma), SH-SY5Y (human bone-marrow neuroblastoma), PC-12 (rat adrenal gland pheochromocytoma), and HeLa (human epithelial cervix adenocarcinoma). Moreover, formation of a 3D coculture model was successfully observed by using MDA-MB-231 dsRED and MDA-MB-231 GFP cells. Taken together, these results indicate that the developed MagLev setup provides an easy and efficient way to fabricate 3D cellular structures and may be a feasible alternative to conventional methodologies for cellular/multicellular studies.

Termičko ponašanje I biološka aktivnost [Co2(Cl)2 TPMC](BF4)2 kompleksa

A large number of interesting Co (II) complexes with macrocyclicligands have been synthesized and the recognition of its complexes as important bioactive compounds in vitro and in vivo has aroused growing interest in these agents as potential drugs for therapeutic use in various diseases. Numerous available information on their bioinorganic properties and mode of action in several biological systems, combined with the new possibilities imposed by the development of medical chemistry, opens space for the development of a new generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to present some properties of the earlier isolated the first Co(II)tpmc complex for which crystal structure confirmed chair conformation of macrocycle. Complex with formula (Co2(Cl)2tpmc)(BF4)2 (tpmc = N,N`,N``,N```tetrakis(2-pyridylmethyl)-1,4,8,11 - tetraazacyclotetradecane), was studied on thermal behaviour and biological activity. TG-DTA analysis indicates that complex decomposition in a single step in the range of 365 -435 °C. Investigated cytotoxic activity against two human cancer cell lines: HeLa (human cervix adenocarcinoma) and K562 (human myelogenous leukaemia). Complex was also preliminary assayed in vitro toward bacteria, fungi and mould together with the starting material for the synthesis (ligands, simple salts and solvents) as test substances. Investigated complex showed a moderate activity against strains of bacteria and were inactive against the tested fungi and mould. Minimal inhibitory concentration suppressing the visible growth of bacteria was determined. Biological investigations show the complex has significant cytotoxic potential.

Investigation of nanoformulation and incorporation potential of radiolabeled curcumin using HeLa and MDAH-2774 cells

Nowadays plant origin compounds with anti-cancer properties come into prominence, among them is curcumin (CUR) with a remarkable anti-cancer activity against various cancers. CUR was nanoformulated (CUR-PLGA) by the polymer based poly(lactic-co-glycolic acid) (PLGA) and both CUR and CUR-PLGA were radiolabeled with iodine-131 radionuclide for investigation of their in vitro behaviour on Human cervix adenocarcinoma (HeLa) and Ovarian endometrioid adenocarcinoma (MDAH-2774) cell lines. The newly described radiolabeled CUR and CUR-PLGA may be initiative discovery of novel potential imaging and therapeutic agents.

Four triorganotin(IV) esters based on 3,5-bifluorobenzenetelluronic acid: Syntheses, structures, in vitro cytostatic activity and BSA-binding assessment

Four novel 3,5-bifluorobenzenetelluronic triorganotin(IV) esters, namely (3,5-F2C6H3TeOH)2(μ-O)2(OSnR3)4 (R = Me: 1, R = Ph: 2) and (3,5-F2C6H3TeOH)(OSnR3)4 (R = Me: 3, R = Ph: 4) have been synthesized and characterized by the reaction of deprotonated 3,5-bifluorobenzenetelluronic acid ligand and corresponding R3SnCl (R = Me, Ph). All the complexes have been characterized by means of elemental analysis, FT-IR, NMR (1H, 13C, 119Sn) spectroscopy, and X-ray crystallography. Structural analyses of these complexes reveal that complexes 1 and 2 exhibit centrosymmetric dimeric structure with an almost planar four-membered Te2(μ2-O)2 core in the center, while 3 and 4 form monomeric structure with a single Te center. The Te atoms adopt octahedral geometry in all the complexes. Complexes 1–4 could form 2D or 3D supramolecular structures through intermolecular C-H···F or C-H···O interactions. Preliminary in vitro cytostatic studies show that complexes 1–4 exhibit effective cytostatic activity against human cervix adenocarcinoma cell lines (HeLa) and human hepatocellular carcinoma cell lines (HepG-2). For further assessing apoptosis properties of complex 2, the levels of apoptosis were examined. The BSA-binding properties were investigated by means of fluorescence titration. The results indicate that complexes 1–4 could quench the intrinsic fluorescence of BSA.