Abstract
In the course of our studies to identify novel natural calmodulin inhibitors [1], the new xanthones 15-chlorotajixanthone hydrate (1), 14-methoxytajixanthone (2), shamixanthone (3) and tajixanthone hydrate (4) were isolated and identified from the new fungus Emericella sp. strain 25379. The activation of the calmodulin-sensitive cAMP phosphodiesterase (PDE1) was inhibited in the presence of 1-4 in a concentration-dependent manner. The effect of compounds 2 (IC50=5.54±1.28µM) and 4 (IC50=5.62±1.25µM) were higher than that of chlorpromazine (CZP) (IC50=7.26±1.60µM), a well known CaM inhibitor used as a positive control. The inhibition mechanism of both compounds was competitive with respect to CaM according to a kinetic analysis. A docking analysis with 2 and 4 using the advanced docking program AutoDock 4.0 [2] revealed that both compounds interacted with CaM in the same pocket of trifluoropiperazine (TFP) and CZP.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call