cell toxicity
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2022 ◽  
Vol 15 (1) ◽  
pp. 64
Author(s):  
Ok Kyoung Choi ◽  
Yong Ho Sun ◽  
Hyemi Lee ◽  
Joon Kwang Lee ◽  
Tae Hoon Lee ◽  
...  

A series of (S)-3-(1-aminoethyl)-8-pyrimidinyl-2-phenylisoquinoline-1(2H)-ones 3a–3k was synthesized in 40–98% yield through Suzuki–Miyaura coupling using Pd(PPh3)2Cl2, Sphos, and K2CO3 in THF/H2O mixed solvent. All newly synthesized compounds were evaluated for cell viability (IC50) against MDA-MB-231, HeLa, and HepG2 cells. The antitumor activities of 3a–3k were improved when various pyrimidine motifs were introduced at position C-8 of the isoquinolinone ring.


Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1616
Author(s):  
Tuchakorn Lertwanakarn ◽  
Pirada Trongwongsa ◽  
Sangchai Yingsakmongkol ◽  
Matepiya Khemthong ◽  
Puntanat Tattiyapong ◽  
...  

The outbreak of the novel Tilapia tilapinevirus or Tilapia lake virus (TiLV) is having a severe economic impact on global tilapia aquaculture. Effective treatments and vaccines for TiLV are lacking. In this study, we demonstrated the antiviral activity of ribavirin against TiLV in E-11 cells. Our findings revealed that at concentrations above 100 μg/mL, ribavirin efficiently attenuates the cytopathic effect of the TiLV infection in fish cells. When administered in a dose-dependent manner, ribavirin significantly improved cell survival compared to the untreated control cells. Further investigation revealed that the cells exposed to ribavirin and TiLV had a lower viral load (p < 0.05) than the untreated cells. However, at concentrations above 1000 μg/mL, ribavirin led to cell toxicity. Taken together, our results demonstrate the efficacy of this antiviral drug against TiLV and could be a useful tool for future research on the pathogenesis and replication mechanism of TiLV as well as other piscine viruses.


Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1848
Author(s):  
Jacob Fritzsch ◽  
Alexander Korn ◽  
Dayana Surendran ◽  
Martin Krueger ◽  
Holger A. Scheidt ◽  
...  

Amyloid β (Aβ) is a peptide known to form amyloid fibrils in the brain of patients suffering from Alzheimer’s disease. A complete mechanistic understanding how Aβ peptides form neurotoxic assemblies and how they kill neurons has not yet been achieved. Previous analysis of various Aβ40 mutants could reveal the significant importance of the hydrophobic contact between the residues Phe19 and Leu34 for cell toxicity. For some mutations at Phe19, toxicity was completely abolished. In the current study, we assessed if perturbations introduced by mutations in the direct proximity of the Phe19/Leu34 contact would have similar relevance for the fibrillation kinetics, structure, dynamics and toxicity of the Aβ assemblies. To this end, we rationally modified positions Phe20 or Gly33. A small library of Aβ40 peptides with Phe20 mutated to Lys, Tyr or the non-proteinogenic cyclohexylalanine (Cha) or Gly33 mutated to Ala was synthesized. We used electron microscopy, circular dichroism, X-ray diffraction, solid-state NMR spectroscopy, ThT fluorescence and MTT cell toxicity assays to comprehensively investigate the physicochemical properties of the Aβ fibrils formed by the modified peptides as well as toxicity to a neuronal cell line. Single mutations of either Phe20 or Gly33 led to relatively drastic alterations in the Aβ fibrillation kinetics but left the global, as well as the local structure, of the fibrils largely unchanged. Furthermore, the introduced perturbations caused a severe decrease or loss of cell toxicity compared to wildtype Aβ40. We suggest that perturbations at position Phe20 and Gly33 affect the fibrillation pathway of Aβ40 and, thereby, influence the especially toxic oligomeric species manifesting so that the region around the Phe19/Leu34 hydrophobic contact provides a promising site for the design of small molecules interfering with the Aβ fibrillation pathway.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1979
Author(s):  
Blessing Mabate ◽  
Chantal Désirée Daub ◽  
Samkelo Malgas ◽  
Adrienne Lesley Edkins ◽  
Brett Ivan Pletschke

Although there are chemotherapeutic efforts in place for Type 2 diabetes mellitus (T2DM), there is a need for novel strategies (including natural products) to manage T2DM. Fucoidan, a sulphated polysaccharide was extracted from Ecklonia radiata. The integrity of the fucoidan was confirmed by structural analysis techniques such as FT-IR, NMR and TGA. In addition, the fucoidan was chemically characterised and tested for cell toxicity. The fucoidan was investigated with regards to its potential to inhibit α-amylase and α-glucosidase. The fucoidan was not cytotoxic and inhibited α-glucosidase (IC50 19 µg/mL) more strongly than the standard commercial drug acarbose (IC50 332 µg/mL). However, the fucoidan lacked potency against α-amylase. On the other hand, acarbose was a more potent inhibitor of α-amylase (IC50 of 109 µg/mL) than α-glucosidase. Due to side effects associated with the use of acarbose, a combination approach using acarbose and fucoidan was investigated. The combination showed synergistic inhibition (>70%) of α-glucosidase compared to when the drugs were used alone. The medicinal implication of this synergism is that a regimen with a reduced acarbose dose may be used, thus minimising side effects to the patient, while achieving the desired therapeutic effect for managing T2DM.


Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1378
Author(s):  
Wen-Jung Lu ◽  
Pang-Hung Hsu ◽  
Chun-Ju Chang ◽  
Cheng-Kuan Su ◽  
Yan-Jyun Huang ◽  
...  

Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC50 and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant E. coli. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant Escherichia coli. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant E. coli, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant E. coli. Additionally, DPM did not seem to damage the E. coli membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant E. coli.


2021 ◽  
pp. 2101854
Author(s):  
Siyuan Xiang ◽  
Jessica Wagner ◽  
Thorsten Lückerath ◽  
Klaus Müllen ◽  
David Y. W. Ng ◽  
...  
Keyword(s):  

Author(s):  
João Pessoa

Apoptosis dysfunction is associated with several malignancies, including cancer and autoimmune diseases. Apoptosis restoration could be an attractive therapeutic approach to those diseases. Mitochondrial outer membrane permeabilization is regarded as the point of no return in the ‘classical’ apoptosis triggering pathway. Cytoplasmic release of cytochrome c (cyt c), a mitochondrial electron transporter, is a prominent indicator of such critical step. Therefore, visualizing cyt c efflux in living cells is a convenient approach to address apoptosis triggering and monitor performance of apoptosis restoration strategies. Recent years have been prolific in the development of biosensors to visualize cyt c mitochondrial efflux in living cells, by fluorescence microscopy. These biosensors specifically detect endogenous, untagged cyt c, while showing efficient cellular uptake and reduced cell toxicity. A common aspect is their fluorescence quenching in the absence or presence of bound cyt c, resulting in two main biosensor types: ‘turn ON’ and ‘turn OFF’. In some of these systems, fluorescence intensity of fluorophore-bound aptamers is enhanced upon cyt c binding. In others, cyt c binding to quantum dots quenches their fluorescence. In the present minireview, I describe these biosensors and briefly introduce some hypotheses that could be addressed using these novel tools.


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