Abstract
Reaction of compound 1 with dimethylformamide dimethylacetal gave enaminone 2, which reacts with 1,4-benzoquinone and 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one to afford 6 and 7, respectively. Treatment of 2 with hydroxylamine hydrochloride gave cyanoacetyl derivative 14. Enaminone 2 reacts with guanidine hydrochloride and phenylhydrazine to furnish 2-aminopyrimidine and pyrazole derivatives 15 and 16, respectively. Enaminone 2 also reacts with ethylenediamine and acetylacetone to afford the corresponding derivatives of 1,4-diazepine 18 and pyridine 20, respectively. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, H-1 NMR, C-13 NMR and MS spectral data. All the synthesized compounds were evaluated for antimicrobial activity. Compounds 6 and 20 were found to be highly active against the all microorganisms. In addition, all the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 14, 6, 18 and 16 with selectivity index (SI) values of 70.92, 55.56, 29.56 and 15.00, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 13.30. Virtual screening using molecular docking studies of the synthesized compounds was performed by Molecular Operating Environment (MOE). The results indicated that some synthesized compounds suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.