Abstract
BackgroundDesign and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN).ResultsThe synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L.ConclusionIn-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins.
Highlights
Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents
The pyrazole-dimedone derivatives were prepared as shown in Scheme 1 via one pot Knoevenagel condensation Michael addition of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, 1,3-dicarbonyl compound and various aldehydes mediated by aqueous NHEt2
This one pot multicomponent reaction afforded the final targets as hybrid frameworks 4a–o in good yields (40–78%) with substrate tolerance of pyrazoledimedone derivatives
Summary
Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). Dimedone has been utilized successfully as pharmacophoric building block in various antimicrobial agents such as xanthenes [14, 15], substituted chromenes [16], macrocyclic metal complexes [17], quinazoline derivatives [18], tetrahydro quinolone diones [19] and acridine based compounds [20]. Recognizing these facts and in continuation of our previous work [12, 13] new hybrid molecules incorporating pyrazoles and dimedone in a single molecular framework were designed and synthesized. We subjected our target compounds to pharmacophore modeling and molecular docking on different target proteins to explore their mode of action
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