Synthesis of enamine derivatives bearing of 2H-pyran-2,4(3H)-dione moiety from dehydroacetic acid: A promising frontier in skin protection and anti-aging, in-vitro, and in-silico insights

Abstract

In aging research, the most crucial objective is to find longevity-enhancing drugs and analyze their subsequent mode of action. Search for longevity-enhancing drugs and their targets is, however, very challenging. The current study aimed to synthesize novel enamine-based derivatives as anti-aging products. The structures of these derivatives were characterized using multinuclear nmR (1H, 13C, and DEPT-135), mass spectrometry, single crystal XRD, and elemental analysis. Almost all the derivatives 3a-g showed good to excellent activities against elastase enzyme more than the reference drug. The IC50 value of compounds 3e and 3f (0.8 ± 0.2 µM and 0.7 ± 0.4 µM resp.) make them the most potent derivatives against elastase enzyme. Compound 3f exhibited prominent free radical scavenging activity (95.7%) and showed a zone of inhibition (24 mM/100 µL) against candida albicans. The docking studies showed that derivative 3b has the lowest binding affinity (-8.8 kcal/mol) and the best fitting orientation in the active pocket of the elastase enzyme. We infer from the biological activity results that some derivatives can be skin-protecting agents.