Next Article in Journal
Quantitative Assessment of the Environmental Impacts of Dredging and Dumping Activities at Sea
Next Article in Special Issue
New Local Drug Delivery with Antibiotic in the Nonsurgical Treatment of Periodontitis—Pilot Study
Previous Article in Journal
Robot Swarm Navigation and Victim Detection Using Rendezvous Consensus in Search and Rescue Operations
Open AccessArticle

Synthesis, Tyrosinase Inhibiting Activity and Molecular Docking of Fluorinated Pyrazole Aldehydes as Phosphodiesterase Inhibitors

1
Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, Vladimira Preloga 1, 31000 Osijek, Croatia
2
Faculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Franje Kuhača 20, 31000 Osijek, Croatia
3
Department of Biology, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, 31000 Osijek, Croatia
*
Author to whom correspondence should be addressed.
Appl. Sci. 2019, 9(8), 1704; https://doi.org/10.3390/app9081704
Received: 6 March 2019 / Revised: 5 April 2019 / Accepted: 19 April 2019 / Published: 25 April 2019
A series of fluorinated 4,5-dihydro-1H-pyrazole derivatives were synthesized in the reaction of corresponding acetophenone and different aldehydes followed by the second step synthesis of desired compounds from synthesized chalcone, hydrazine hydrate, and formic acid. Structures of all compounds were confirmed by both 1H and 13C NMR and mass spectrometry. Antibacterial properties of compounds were tested on four bacterial strains, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Among synthesized compounds, the strongest inhibitor of monophenolase activity of mushroom tyrosinase (32.07 ± 3.39%) was found to be 5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde. The PASS program has predicted the highest probable activity for the phosphodiesterase inhibition. To shed light on molecular interactions between the synthesized compounds and phosphodiesterase, all compounds were docked into the active binding site. The obtained results showed that the compound with the dimethoxyphenyl ring could be potent as an inhibitor of phosphodiesterase, which interacts in PDE5 catalytic domain of the enzyme. Key interactions are bidentate hydrogen bond (H-bond) with the side-chain of Gln817 and van der Waals interactions of the dimethoxyphenyl ring and pyrazole ring with hydrophobic clamp, which contains residuals, Val782, Phe820, and Tyr612. Interactions are similar to the binding mode of the inhibitor sildenafil, the first oral medicine for the treatment of male erectile dysfunction. View Full-Text
Keywords: fluorinated pyrazole aldehydes; tyrosinase inhibition; phosphodiesterase inhibition; antibacterial activity; molecular docking fluorinated pyrazole aldehydes; tyrosinase inhibition; phosphodiesterase inhibition; antibacterial activity; molecular docking
Show Figures

Graphical abstract

MDPI and ACS Style

Rastija, V.; Brahmbhatt, H.; Molnar, M.; Lončarić, M.; Strelec, I.; Komar, M.; Pavić, V. Synthesis, Tyrosinase Inhibiting Activity and Molecular Docking of Fluorinated Pyrazole Aldehydes as Phosphodiesterase Inhibitors. Appl. Sci. 2019, 9, 1704.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop