Novel 1-morpholine-3-substituted triazol-5-ones: Synthesis and multi-biological evaluation on HepG2 and U87 cells with SAR and DFT studies

Abstract

The biologically active novel 1-morpholine-3-substitue-4-(4-phenylacetoxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 4(a-f) were successfully synthesized and structurally characterized by 1H /13C NMR, and FT-IR spectroscopy. Concentration ranges of 31.25, 62.5, 125, 250, and 500 µg/mL were applied to determine the anti-cancer properties of compund. Significant results were obtained against the human hepatoma cells HepG2 and human glioblastoma cell line U87. Antioxidant activities were assessed in vitro using DPPH radical scavenging and metal chelation assays and it was seen that compounds 4(a-f) had metal chelating properties. Furthermore, the enzyme inhibitory effect of compounds on α-amylase (α-Amy), α-glucosidase (α-Gly), glutathione S-transferase (GST), acetylcholinesterase (AChE) enzymes were studied. IC<inf>50</inf> values were calculated in different ranges. The antimicrobial properties were investigated using the Agar-well diffusion technique. The compounds had antimicrobial activity against 5 bacteria except Escherichia coli, and especially the inhibition zone diameter of compound 4e against Bacillus cereus was found to be the highest with a measurement of 24 mm. Complementary density functional theory (DFT) calculations and structure-activity relationship (SAR) analyses were performed to provide insights into the molecular properties and biological activities of the synthesized Mannich bases. © 2025 Elsevier B.V., All rights reserved.