Structural Studies on Bioactive Compounds. 30. Crystal Structure and Molecular Modeling Studies on thePneumocystis cariniiDihydrofolate Reductase Cofactor Complex with TAB, a Highly Selective Antifolate†,‡,§

Biochemistry ◽  
2000 ◽  
Vol 39 (13) ◽  
pp. 3556-3564 ◽  
Author(s):  
Vivian Cody ◽  
David Chan ◽  
Nikolai Galitsky ◽  
Dawn Rak ◽  
Joseph R. Luft ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Modeling ◽  
Bioactive Compounds ◽  
Structural Studies ◽  
Modeling Studies ◽  
Molecular Modeling Studies

scholarly journals Crystal Structure and Mechanistic Molecular Modeling Studies of Mycobacterium tuberculosis Diterpene Cyclase Rv3377c

Biochemistry ◽  
2020 ◽  
Vol 59 (47) ◽  
pp. 4507-4515
Author(s):  
Yue Zhang ◽  
Lisa M. Prach ◽  
Terrence E. O’Brien ◽  
Frank DiMaio ◽  
Daniil M. Prigozhin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Molecular Modeling ◽  
Modeling Studies ◽  
Diterpene Cyclase ◽  
Molecular Modeling Studies

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

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
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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