Solvent free synthesis, characterization, anticancer, antibacterial, antifungal, antioxidant and SAR studies of novel (E)-3-aryl-1-(3-alkyl-2-pyrazinyl)-2-propenone

Abstract

Two series of novel (E)-3-aryl-1-(3-alkyl-2-pyrazinyl)-2-propenones (3a–3f and 3g–3l) have been synthesized by the Claisen–Schmidt condensation reaction between 2-acetyl-3-alkyl pyrazine (0.005 mol, 1a–1b) and para-substituted aromatic aldehydes (0.005 mol, 2a–2f) under solvent-free K₂CO₃ solid supported microwave environment, with 90–95% yield. The structures were confirmed by FTIR, ¹H NMR, ¹³C NMR, LCMS (Q-TOF) and elemental analysis. The mean surface roughness values (R_a) of 10.59 and 10.87 nm for 3c and 3i, respectively, were measured with AFM. Compounds were tested for their in vitro anticancer activity against the MCF-7 cell line using sulforhodamine B (SRB) assay protocols to estimate cell growth and compared with adriamycin. Compound 3i containing p-Br on the phenyl ring expressed promising anticancer activity (GI₅₀ ≤ 0.1 μM). The cytotoxicity (LC₅₀) was found in the range of 86 to >100 μM as compared to that of the standard (LC₅₀ = 89 μM). Also, compounds were screened for in vitro antibacterial and antifungal activities, and the most prominent effects were observed with 3a, 3c, 3d and 3e against gram-positive and gram-negative strains. Compounds 3a–3l showed 30–66% antioxidant activities, determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method. The viscosity as a transport property was studied for their entire composition range at 298.15 K. Data were regressed against concentration for limiting viscosity and noted as 3h > 3g > 3i = 3l > 3k > 3a > 3j > 3f > 3e > 3c > 3d > 3b.