Synthesis of novel antioxidant and antitumor 5-aminopyrazole derivatives, 2D/3D QSAR, and molecular docking.

5-Aminopyrazole serves as a vital precursor for several biologically active pyrazoloazines, including pyrazolopyridine, pyrazolopyrimidine, and pyrazolotriazine, as well as Schiff bases, thiourea, and phthalimide derivatives. In this study, we structurally characterized novel pyrazole derivatives by spectral IR, 1H and 13C NMR, and MASS spectroscopy. We also evaluated antioxidant activity of various derivatives using ABTS and DPPH methods and cytotoxicity in the hepatocellular carcinoma Hep-G2 cells by SRB assay. The most potent antitumor molecules were 5-aminopyrazole derivative 3, chloroacetanilide derivative 8, maleimide derivative 10a, pyrazolopyrimidine 16, and enamine 19, with IC50 values of 41, 3.6, 37, 24.4, and 17.7 µM, respectively. Complementary computational studies predicted QSAR and bioactivity of these molecules. Interestingly, the most effective compounds were also predicted to be kinase inhibitors; in addition, molecular docking with liver receptors (3MBG, 4XCU, and 4G9C) predicted promising interactions.

Synthesis, characterization, antibacterial evaluation, 2D-QSAR modeling and molecular docking studies for benzocaine derivatives.

Possible application of incorporating a well-known drug (benzocaine) with cyanoacetamide function to get a powerful synthon ethyl 4-cyanoacetamido benzoate. This synthetic intermediate was used as a precursor for the synthesis of triazine, pyridone, thiazolidinone, thiazole and thiophene scaffolds containing the benzocaine core. Facile coupling, Michael addition, condensation and nucleophilic attack reactions were used to synthesize our targets. The structural features of the synthesized scaffolds were characterized using IR, 1H NMR, 13C NMR and mass spectroscopy. The antibacterial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) were evaluated using ampicillin as a reference drug. DNA/methyl-green colorimetric assay of the DNA-binding compounds was also performed. Theoretical studies of the newly synthesized compounds based on molecular docking and QSAR study were conducted. The molecular docking studies were screened by MOE software for the more potent antibacterial agent 28b and each native ligand against four of S. aureus proteins 1jij, 2xct, 2w9s and 3t07.

Synthesis, biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles.

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.