Synthesis and pharmacological properties of coumarin-chalcones

Abstract

New chalcones (2a-e) were prepared by Claisen-Schmidt condensation from 3-acetyl-4-hydroxycoumarin, which was used as a key intermediate in this synthesis. However, we can easily obtain compounds (3a-e) by refluxing chalcone (2a-e) with 4-hydroxycoumarin in the presence of ammonium acetate and glacial acetic acid. Multinuclear NMR (¹H and ¹³C), IR and elemental analysis characterized the structure of the final compound. The antibacterial activity of the obtained products against various bacterial strains was tested in vitro. The antioxidant properties of the same synthesized compounds were also studied using DPPH (2,2-diphenyl-1-trinitrophenylhydrazine) and hydroxyl radical scavenging tests. Furthemore a study was conducted to highlight the nature of the effects produced by screening 2a-e and 3a-e products on colon cancer cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2). Good cytotoxic activity against standard vinblastine was observed for compound 3a. •3-acetyl-4-hydroxycoumarin as a simple coumarinic ketone was modified to coumarins-bonded chalcones.•Modification was performed through two steps reaction.•Final products exhibited free radical scavenging activity and Good cytotoxic.

Keywords: Anti-inflammatory activity and antiproliferative activity; Antibacterial; Antioxidant; Coumarin; Coumarin chalcones hybrids; Synthesis of coumarin -bonded chalcone derivatives via two steps reaction.

Graphical abstract

Fig. 1

Zone of bacterial inhibition measured in mm of the synthesized chalcones 2a-e and compounds 3a-e.

Scheme 1

Basic structure of chalcone (middle) and some naturally occurring chalcones.

Scheme 2

Protocol synthesis of compounds 3a-3e.

Scheme 3

Plausible reaction mechanism for the formation of compounds 3.

Fig. 2

Antioxydant activity of the synthesized compounds 2a-e et 3a-e assessed by DPPH and ABTS techniques and expressed as IC₅₀ in mg mL⁻¹. The BHT was used as control.

Fig. 3

IC₅₀ values of the compounds 2a-e and their compounds 3a-e for anti-inflammatory activity.

Fig. 4

Evaluation of cytotoxicity of the synthesized compounds (2a-2e) and (3a-3e) against colon carcinoma cells (HCT-116).

Fig. 5

Evaluation of cytotoxicity of the synthesized compounds (2a-2e) and (3a-3e) against hepatocellular carcinoma cells lines (HepG-2).

Fig. 6

IC₅₀ of the synthesized compound (2a-2e) and (3a-3e) on colon carcinoma cells (HCT-116) and hepatocellular carcinoma cells lines (HepG-2).