Synthesis, characterization, in-vitro and in-silico therapeutic studies of cinnamaldehyde derivatives

Cinnamomum verum (cinnamon) is a versatile spice belonging to the family Lauraceae. The plant is widely used for its various therapeutic potential viz. antimicrobial, antioxidant, anti-inflammatory, anti-diabetic, anticancer, etc. Its phytocompounds render these therapeutic efficacies of cinnamon. Cinnamaldehyde is the main active compound of cinnamon. Owing to the numerous pharmacology of cinnamaldehyde, cinnamaldehyde was procured from Himedia. Cinnamaldehyde Schiff bases were synthesized by refluxing (40–60 °C) cinnamaldehyde with different primary amines for 4–6 h. Glacial acetic acid was used as a catalyst. The product confirmation was done based on thin-layer chromatography. The derivatives were characterized and investigated for antimicrobial (disc-diffusion and broth-dilution methods), antioxidant (DPPH and ABTS assays), and cytotoxicity activities (SRB assay). Higher antibacterial activities were noticed with compounds, NS-6A (ZIsa = 13.7 ± 2.05 mm) and E.O.A (MICec, pa = 6.25 mg/mL) whereas the maximum antifungal results were observed with E.O.A (ZIfo = 13.1 ± 0.14 mm), MCA (MICao = 6.25 mg/mL) by. Compounds MCA (% RSADPPH = 85.35, % RSAABTS = 92.26), E.O.A (% RSADPPH = 83.81, % RSAABTS = 90.54) and NS-9A (% RSADPPH = 83.42, % RSAABTS = 90.32) showed highest antioxidant activity. The highest cytotoxicity against the HCT-116 cell line was observed in compounds MCA (IC50 = 0.27 µg/mL), and E.O.A (IC50 = 0.38 µg/mL). Compound NS-4A was observed with the highest docking score (-8.527). Conclusively, E.O.A, MCA, and NS-9A were the most potent compounds and need further in-depth exploration. © 2024 Elsevier B.V.