A Six Coordinated Phosphorus(V) Corrole Bearing Two Hydroxyl Axial Ligands: X‐Xay Structure, DNA Interaction, Photonuclease Activity, and Cytotoxicity towards Tumor Cells

2021 ◽  
Vol 6 (32) ◽  
pp. 8200-8204
Author(s):  
Xiao Jiang ◽  
Yan‐Mei Sun ◽  
Jing‐He Cen ◽  
Wu Yang ◽  
Yu‐Hui Liao ◽  
...  
Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4519 ◽  
Author(s):  
Jiahe Li ◽  
Rongping Liu ◽  
Jinzhang Jiang ◽  
Xing Liang ◽  
Ling Huang ◽  
...  

A series of ZnCl2 complexes (compounds 1–10) with 4′-(substituted-phenyl)-2,2′:6′,2′′-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) μM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3471
Author(s):  
Xia Hu ◽  
Ning-Yi Liu ◽  
Yuan-Qing Deng ◽  
Shan Wang ◽  
Ting Liu ◽  
...  

The photophysical and biological properties of two new phenanthroline-based ligand ruthenium complexes were investigated in detail. Their DNA interaction modes were determined to be the intercalation mode using spectra titration and viscosity measurements. Under irradiation, obvious photo-reduced DNA cleavages were observed in the two complexes via singlet oxygen generation. Furthermore, complex 2 showed higher DNA affinity, photocleavage activity, and singlet oxygen quantum yields than complex 1. The two complexes showed no toxicity towards tumor cells (HeLa, A549, and A375) in the dark. However, obvious photocytotoxicities were observed in the two complexes. Complex 2 exhibited large PIs (phototherapeutic indices) (ca. 400) towards HeLa cells. The study suggests that these complexes may act as DNA intercalators, DNA photocleavers, and photocytotoxic agents.


2018 ◽  
Vol 47 (21) ◽  
pp. 7144-7158 ◽  
Author(s):  
Salvatore Savino ◽  
Valentina Gandin ◽  
James D. Hoeschele ◽  
Cristina Marzano ◽  
Giovanni Natile ◽  
...  

DNA and mitochondria of tumor cells are the targets of Pt(iv) complexes of kiteplatin with biologically active dichloroacetate as axial ligands.


Author(s):  
D.P. Bazett-Jones ◽  
F.P. Ottensmeyer

Dark field electron microscopy has been used for the study of the structure of individual macromolecules with a resolution to at least the 5Å level. The use of this technique has been extended to the investigation of structure of interacting molecules, particularly the interaction between DNA and fish protamine, a class of basic nuclear proteins of molecular weight 4,000 daltons.Protamine, which is synthesized during spermatogenesis, binds to chromatin, displaces the somatic histones and wraps up the DNA to fit into the small volume of the sperm head. It has been proposed that protamine, existing as an extended polypeptide, winds around the minor groove of the DNA double helix, with protamine's positively-charged arginines lining up with the negatively-charged phosphates of DNA. However, viewing protamine as an extended protein is inconsistent with the results obtained in our laboratory.


Author(s):  
C. N. Sun ◽  
C. Araoz ◽  
H. J. White

The ultrastructure of a cerebral primitive neuroectodermal tumor has been reported previously. In the present case, we will present some unusual previously unreported membranous structures and alterations in the cytoplasm and nucleus of the tumor cells.Specimens were cut into small pieces about 1 mm3 and immediately fixed in 4% glutaraldehyde in phosphate buffer for two hours, then post-fixed in 1% buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate.In the cytoplasm of the tumor cells, we found paired cisternae (Fig. 1) and annulate lamellae (Fig. 2) noting that the annulate lamellae were sometimes associated with the outer nuclear envelope (Fig. 3). These membranous structures have been reported in other tumor cells. In our case, mitochondrial to nuclear envelope fusions were often noted (Fig. 4). Although this phenomenon was reported in an oncocytoma, their frequency in the present study is quite striking.


Author(s):  
J. C. Garancis ◽  
J. F. Kuzma ◽  
S. D. Wilson ◽  
E. H. Ellison

It has been proposed that a gastrin-like hormone elaborated by non-beta islet tumors of the pancreas may be responsible for a fulminating ulcer diathesis. Subsequently, a potent gastric secretagogue was isolated from ulcerogenic tumors of the pancreas. This disease process is known now as “Zollinger-Ellison syndrome”.In our studies of two cases of Zollinger-Ellison syndrome, pancreatic lesions were identified as alpha islet cell tumors (Fig. 1). Tumor cells were fairly uniform. The sizes of the alpha granules were not significantly different, but their number and distribution varied greatly from one cell to another. Each granule consisted of a round, highly dense central core, separated from the limiting membrane by an opaque zone. The granular form of the endoplasmic reticulum was particularly prominent. Numerous mitochondria, round or elongated, were dispersed throughout the cytoplasm. Individual or clusters of lysosomes were observed in the majority of cells.


Author(s):  
Krishan K. Arora ◽  
Glenn L. Decker ◽  
Peter L. Pedersen

Hexokinase (ATP: D-hexose 6-phophotransferase EC 2.7.1.1) is the first enzyme of the glycolytic pathway which commits glucose to catabolism by catalyzing the phosphorylation of glucose with ATP. Previous studies have shown diat hexokinase activity is markedly elevated in rapidly growing tumor cells exhibiting high glucose catabolic rates. A large fraction (50-80%) of this enzyme activity is bound to the mitochondrial fraction (1,2) where it has preferred access to ATP (3). In contrast,the hexokinase activity of normal tissues is quite low, with one exception being brain which is a glucose-utilizing tissue (4). Biochemical evidence involving rigorous subfractionation studies have revealed striking differences between the subcellular distribution of hexokinase in normal and tumor cells [See review by Arora et al (4)].In the present report, we have utilized immunogold labeling techniques to evaluate die subcellular localization of hexokinase in highly glycolytic AS-30D hepatoma cells and in the tissue of its origin, i.e., rat liver.


Author(s):  
C.D. Bucana ◽  
R. Sanchez ◽  
R. Singh ◽  
I.J. Fidler

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.


Author(s):  
John R. Palisano

Although confronting cistemae (CC) have been observed in a variety of tumor cells and normal fetal rat, mouse, and human epithelial tissues, little is known about their origin or role in mitotic cells. While several investigators have suggested that CC arise from nuclear envelope (NE) folding back on itself during prophase, others have suggested that CC arise when fragments of NE pair with endoplasmic reticulum. An electron microscopic investigation of 0.25 um thick serial sections was undertaken to examine the origin of CC in HeLa cells.


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