TY  - BOOK
AU  - Figueroa,M.
AU  - González,M.C.
AU  - Rodríguez-Sotres,R.
AU  - Sosa-Peinado,A.
AU  - González-Andrade,M.
AU  - Cerda-García-Rojas,C.M.
AU  - Mata,R.
TI  - Calmodulin inhibitors from the fungus Emericella sp
KW  - EMERICELLA
KW  - 15-CHLOROTAJIXANTHONE HYDRATE
KW  - 14-METHOXYTAJIXANTHONE
KW  - SHAMIXANTHONE
KW  - TAJIXANTHONE HYDRATE
KW  - CALMODULIN
KW  - DOCKING
N2  - 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 lM)and 4 (IC50 = 5.62 lM)was comparable with that of chlorpromazine (CPZ; IC50 = 7.26 lM), 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)
UR  - https://drive.google.com/file/d/1TmqZ5JCdqlo1Z_mMC0OvpQkrP1t2dLe7/view?usp=drivesdk
ER  -