Fuente: PubMed "medicinal and aromatic plants" RSC Adv. 2026 Jul 3. doi: 10.1039/d6ra03816f. Online ahead of print.ABSTRACTA new series of 1-ethoxycarbonyl-3,5-bis(benzyl/alkyl vanillin)-4-piperidone analogues were synthesized via a two-step process involving aldol condensation of vanillin with 1-ethoxycarbonyl-4-piperidone, followed by O-alkylation using diverse aromatic and aliphatic halides. Structural characterization of the resulting compounds (3 and 4a-4m) was confirmed by NMR and HR-MS analyses. Among the synthesized derivatives, compounds 3 and 4k exhibited the most potent and selective cytotoxicity. Compound 3 demonstrated IC50 values of 2.97 µM (SKBR3), 4.4 µM (DU145), and 20.5 µM (HEK-293), while compound 4k showed strong activity against HepG2 (2.27 µM) and DU145 (5.01 µM). Genotoxic assessment revealed that 4k maintained a favourable safety profile, with chromosomal aberration and micronucleus frequencies remaining low or only mildly elevated at higher doses, and a moderate, dose-dependent decrease in mitotic index. Mechanistic studies indicated G0/G1 cell cycle arrest in CHO-K1, DU145, and HepG2 cells, along with significant apoptosis induction in HepG2 (Sub-G1: 13.9%). Although its antioxidant potential was moderate relative to rutin, 4k exhibited dose-dependent free radical scavenging. Antidiabetic screening identified compounds 1, 3, 4c, and 4m as effective α-glucosidase inhibitors (52.6-58.5%; IC50 = 4.27-4.75 µg mL-1), comparable to acarbose. Antimicrobial evaluation showed broad-spectrum activity for compound 1, and compound 4k displayed membrane-stabilizing effects similar to quercetin. In conclusion, these multifunctional vanillin-piperidone hybrids especially compound 4k demonstrate significant anticancer, antidiabetic, and antimicrobial potential, further strengthened by their confirmed non-genotoxic profile.PMID:42405051 | PMC:PMC13330124 | DOI:10.1039/d6ra03816f