Novel bioactivity of furanochromene & coumarin from psoralea corylifolia seeds and their synthetic analogues on skin fibroblast cells

Abstract

Structures derived from natural products have led to discovery of numerous drug leads in modern-day drug development process. Here, we report a new class of compounds that we term Fc-metabolites, reported for the first time from a natural source. Complete structure of the first furanochromene (9H-furo [3,2¿f] chromene; abbreviated as Fc-8b) and furanocoumarin (abbreviated as Fc-8f) are described based on 1H, 13C, 2D-COSY nuclear magnetic resonance spectroscopy and mass spectrometer. Furanochromenes are most related to the furanocoumarins class of compounds. We have developed their purification and identification procedures from the seeds of the legume plant, Psoralea corylifolia that is found commonly in Asia, to produce more than 99% pure compounds. More significantly, we report that these Fc-metabolites are highly active in inducing proliferation of primary human skin cells at concentrations as low as 5 µM. The level of proliferation induced by these compounds is comparable to that by the universal standard 10% fetal calf serum (FCS) in the same time-period. We found that therapeutically, these compounds have wide range of applications but our initial study had few disadvantages such as, these compounds have short shelf-life period and the concentrations of the active compounds purified was very low. These disadvantages led us to the second part of our study.

Availability of structural information from these two bioactive Fc-metabolites shows that the furan and pyran rings are involved in isomerisation. These provide a structural basis for synthesizing further synthetic bioactive furanochromenes (Fc-compounds). Based on the available structure we have developed a novel scheme to synthesize furanocoumarins and furanochromenes. Using this scheme we have synthesized two new furanocoumarin derivatives, of which one is active (Syn 1) and even better in inducing proliferation than natural forms reported here. The cellular level studies show that these bioactive drugs trigger the proliferations mechanism via the G2/M phase of the cell cycle.