Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies

Abstract

A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt 2 . The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program.

Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures

“…1 a Best query displaying pharmacophoric features shared by active lead compounds as colored spheres (cyan for hydrogen bond acceptor function with metal ligator (F1: Acc& ML), pink for hydrogen bond acceptor/donor function with metal ligator (F2: Don, Acc& ML) as well as cyan for hydrophobic region with aromatic centre, hydrogen bond acceptor or metal ligator function (F3: ML/Hyd/Aro/Acc). b Validation of the selected query; mapping of previously reported active compounds 4a and 4n [ 12 ] as well as 4a and 4f [ 13 ], showing RMSD values in acceptable range (0.2823-0.4993). c Mapping of compound 4k on pharmacophore model.…”

“…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.…”

“…Recently, Barakat et al, have been reported novel pyrazole hybrid architectures as efficient antibacterial agents. Various pharmacophores were linked to the pyrazole core to build bioactive scaffolds [ 12 , 13 ]. Within this approach, cyclic dicarbonyl compounds of the type dimedone have attracted our interest.…”

Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

“…5‐Benzylidene BA and TBA show antibacterial activity, as well as an inhibitory effect against mushroom tyrosinase . However, TBA derivatives have been reported to show greater antibacterial activity than those derived from BA . Substitution at C5 increases lipophilicity and hence facilitates the transport of BA and TBA analogues to their enzyme targets …”

Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum

“…Ligand-based screening techniques have the advantage of finding lead molecules based on a set of pharmacophore elements derived from a specific functional ligand family [15,18,19,20]. Owing to the membrane-associated characteristics for all the eukaryotic CYP51s, it remains a challenge to solve their crystal structures.…”