Calmodulin inhibitors from the fungus Emericella sp.
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Mario Figueroa Saldivar, Adjunct Faculty (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
Abstract: Two new xanthones identified as 15-chlorotajixanthone hydrate (1) and 14-methoxytajixanthone (2) were isolated from an Emericella sp. strain 25379 along with shamixanthone (3) and tajixanthone hydrate (4). The stereostructures of 1 and 2 were elucidated by spectroscopic and molecular modeling methods. The absolute configuration at the stereogenic centers of 1 was established according to CD measurements. In the case of 2, however, the absolute configuration at C-20 and C-25 was designated as S and R, respectively, by Mosher ester methodology. Thereafter, the configuration at C-14 and C-15 of 2 was established as S and S, respectively by comparing the optical rotation and 1H–1H coupling constant experimental values with those obtained through molecular modeling calculations at DFT B3LYP/DGDZVP level of theory for diasteroisomers 2a–2d. 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 µM) and 4 (IC50 = 5.62 µM) was comparable with that of chlorpromazine (CPZ; IC50 = 7.26 µM), 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 study. A docking analysis with 2 and 4 using the AutoDock 4.0 program revealed that they interacted with CaM in the same pocket as trifluoropiperazine (TFP).
Calmodulin inhibitors from the fungus Emericella sp.
PDF (Portable Document Format)
618 KB
Created on 11/14/2019
Views: 1125
Additional Information
- Publication
- Bioorganic and Medicinal Chemistry, 17 (6), pp. 2167-2174
- Language: English
- Date: 2009
- Keywords
- Emericella, 15-Chlorotajixanthone hydrate, 14-Methoxytajixanthone, Shamixanthone, Tajixanthone hydrate, Calmodulin, Docking