scholarly journals π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 724
Author(s):  
Sandra Giraldo ◽  
María E. Alea-Reyes ◽  
David Limón ◽  
Asensio González ◽  
Marta Duch ◽  
...  

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6–4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4431-4431
Author(s):  
Yongqian Jia ◽  
Zhen Yan ◽  
Huanling Zhu ◽  
Ting Niu ◽  
Tingting Zeng ◽  
...  

Abstract Imatinib mesylate is a selective tyrosine kinase inhibitor that is effective in the treatment of Philadelphia-positive chronic and acute leukemia. Unfortunately disease recurrence due to drug resistance is still the challenge to obtain cure. To investigate the possible mechanisms of imatinib resistance, we established a BCR/ABL+ cell line with resistance to imatinib (K562-R) by culturing a wild-type K562 cell line (K562-W) in gradually increased concentrations of imatinib over a period of 6 months, which can survive and was maintained in vitro at 3.0 umol/L of imatinib. K562-W and K562-R cells were cultured to logarithmic phase without imatinib, then treated with imatinib at 3.0 umol/L for 2 hours with or without cyclosporin A (2 ug/ml). The cells were washed thoroughly and incubated for further 0, 15, 30 and 60 minutes. Then cell suspensions containing 2×106 cells was measured for imatinib intracellular concentrations by High-Performance Liquid Chromatography (HPLC) after repeated freezing and thawing these cells. The imatinib concentration of K562-W cell is 0.31 umol/L, which is stable even after incubation for 1 hour. The imatinib concentration of K562-R is decreased significantly, being 0.21, 0.08, 0.06 and less than 0.01 umol/L at different incubation times mentioned above. The high level of cyclosporin A showed no effects on imatinib concentrations of both K562-W and K562-R cells. Flow cytometry showed there was no MDR expression of K562-R, whereas there was a small population (about 20%) of K562-W cells with dim expression of MDR. Compared to K562-W cells, the copies of BCR/ABL fusion genes determined by the real-time PCR showed that there were no amplifications of the fusion genes in K562-R cells and BCR/ABL cDNA sequencing showed no mutations of the imatinib ATP binding sites. The western blot assay showed that the expression of heat shock protein 90(Hsp90) was increased in K562-R cells. These results indicate that the intracellular eliminations of imatinib may be one of possible mechanisms for K562-R cells and Hsp90 as a critical molecular chaperone might be involved in the process.


Author(s):  
Aswini A ◽  
Soundhari C

 Objective: Scientists are showing increasing interest in studying fungal endophytes as sources of novel and biologically active compounds. The present study was attempted to isolate and characterize camptothecin (CPT) from endophytic fungus Aspergillus niger isolated from Indian Piper betel plant and detection of its anticancer potential on colon cancer cell line.Methods: The production of CPT was confirmed by high-performance liquid chromatography techniques. The effect of CPT on hematopoietic cell transplantation (HCT) colon cancer cell line was studied by MTT assay.Results: The amount of CPT which is isolated from A. niger was found to be around 0.175 mg/L. Significant death of HCT cells was observed and was non-toxic to normal vero cell line.Conclusion: Hence, CPT can be used as a potential lead compound in cancer research.


1986 ◽  
Vol 108 (1) ◽  
pp. 151-155 ◽  
Author(s):  
H. Suzuki ◽  
A. S. Tischler ◽  
N. D. Christofides ◽  
M. Chretien ◽  
N. G. Seidah ◽  
...  

ABSTRACT High concentrations of a novel pituitary protein (7B2) have been shown to be present in the PC12 rat phaeochromocytoma cell line by radioimmunoassay. 7B2-like immunoreactivity (IR-7B2) was released from PC12 cells into the incubation medium in response to stimulation by a depolarizing concentration of K+, and this K+-evoked release was inhibited by Co2+, The major IR-7B2 in PC12 cell and medium appeared to be identical to that in porcine pituitary gland as judged by both gel permeation chromatography and by reverse-phase high performance liquid chromatography (HPLC). Gel permeation chromatography of extracts of cell and medium revealed two IR-7B2 peaks, the earlier eluting at a elution coefficient (Kav) of 0·30 and the later at a Kav of 0·54. In medium, over 90% of the IR-7B2 eluted as the earlier peak. Fractionation of extracts of cell and medium on reverse-phase HPLC showed three main IR-7B2 peaks eluting at 43, 44·5 and 46% acetonitrile/water with 0·1% trifluoroacetic acid. The findings suggest that IR-7B2 might be released by calcium-mediated exocytosis. J. Endocr. (1986) 108, 151–155


Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 557
Author(s):  
Anna Petruczynik ◽  
Karol Wróblewski ◽  
Justyna Misiurek ◽  
Tomasz Plech ◽  
Karolina Szalast ◽  
...  

Quinolizidine alkaloids exhibit various forms of biological activity. A lot of them were found in the Leguminosae family, including Laburnum and Genista. The aim of the study was the optimization of a chromatographic system for the analysis of cytisine and N-methylcytisine in various plant extracts as well as an investigation of the cytotoxic activities of selected alkaloids and plant extracts obtained from Laburnum anagyroides, Laburnum anagyroides L. quercifolium, Laburnum alpinum, Laburnum watereri, Genista germanica, and Genista tinctoria against various cancer cell lines. The determination of investigated compounds was performed by High Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD), while High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight–Mass Spectrometry (HPLC-QTOF-MS) was applied for the qualitative analysis of plant extracts. The retention, separation selectivity, peaks shape, and systems efficiency obtained for cytisine and N-methylcytisine in different chromatographic systems were compared. The application of columns with alkylbonded and phenyl stationary phases led to a very weak retention of cytisine and N-methylcytisine, even when the mobile phases containing only 5% of organic modifiers were used. The strongest retention was observed when hydrophilic interaction chromatography (HILIC) or especially when ion exchange chromatography (IEC) were applied. The most optimal system in terms of alkaloid retention, peak shape, and system efficiency containing an strong cation exchange (SCX) stationary phase and a mobile phase consisted of 25% acetonitrile and formic buffer at pH 4.0 was applied for investigating alkaloids analysis in plant extracts. Cytotoxic properties of the investigated plant extracts as well as cytisine and N-methylcytisine were examined using human tongue squamous carcinoma cells (SCC-25), human pharyngeal squamous carcinoma cells (FaDu), human triple-negative breast adenocarcinoma cell line (MDA-MB-231), and human breast adenocarcinoma cell line (MCF-7). The highest cytotoxic activity against FaDu, MCF-7, and MDA-MB cancer cell lines was observed after applying the Genista germanica leaves extract. In contrast, the highest cytotoxic activity against SCC-25 cell line was obtained after treating with the seed extract of Laburnum watereri. The investigated plant extracts exhibit significant cytotoxicity against the tested human cancer cell lines and seem to be promising for further research on its anticancer activity.


Sign in / Sign up

Export Citation Format

Share Document