Attenuation of the cytoprotection induced by hypoxic preconditioning upon transfection with BNIP3-siRNA in human neuroblastoma SH-SY5Y cells

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

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Faculty Opinions recommendation of Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091087.544474 ◽

2007 ◽

Author(s):

Gary Rankin

Keyword(s):

Tumor Growth ◽

Human Neuroblastoma

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Faculty Opinions recommendation of Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.4210956.4000054 ◽

2010 ◽

Author(s):

Mark Brincat ◽

Jean Calleja-Agius

Keyword(s):

High Altitude ◽

Chronic Hypoxia ◽

Hypoxic Preconditioning ◽

Metabolic Adaptation

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p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181128112249 ◽

2020 ◽

Vol 17 (2) ◽

pp. 169-183 ◽

Cited By ~ 1

Author(s):

İrem Bozbey ◽

Suat Sari ◽

Emine Şalva ◽

Didem Kart ◽

Arzu Karakurt

Keyword(s):

Molecular Modeling ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Modeling Studies ◽

Broth Microdilution Method ◽

Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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