Cyclodipeptides: From Their Green Synthesis to Anti-Age Activity

Abstract

Cyclodipeptides (CDPs) or diketopiperazines (DKPs) are often found in nature and in foodstuff and beverages and have attracted great interest for their bioactivities, biocompatibility, and biodegradability. In the laboratory, they can be prepared by green procedures, such as microwave-assisted cyclization of linear dipeptides in water, as performed in this study. In particular, five CDPs were prepared and characterized by a variety of methods, including NMR and ESI-MS spectroscopies and single-crystal X-ray diffraction (XRD), and their cytocompatibility and anti-aging activity was tested in vitro, as well as their ability to penetrate the different layers of the skin. Although their mechanism of action remains to be elucidated, this proof-of-concept study lays the basis for their future use in anti-age cosmetic applications.

Keywords: Franz cell; UV-damage; anti-age; cosmetics; cyclodipeptides; diketopiperazines; green synthesis; microwave; peptides; skin absorption.

Figure 1

Five diketopiperazines (DKPs) used in this work.

Figure 2

Crystal packing of DKP1 (CCDC 2203140).

Figure 3

H-bonded ribbons of DKP2 (CCDC 2203142).

Figure 4

Live/dead assay on fibroblast cells cultured with the five DKPs for 24 h.

Figure 5

MTT assay on fibroblast cells cultured with the five DKPs at different concentrations.

Figure 6

Anti-age assay without (ctrl) or with DKPs 1–5 on fibroblast cells, without (top panels) or with (bottom panels) UV exposure. Scalebars = 20 microns.

Figure 7

Quantitative anti-age assay with/without DKPs 1–5 on fibroblast cells. The asterisk denotes p < 0.05 between spread cells (green *) or round cells (gray *).

Figure 8

Quantitative X-Gal assay on UV-treated cells without or with DKPs 1–5. * denotes p < 0.01.