1134426-32-6Relevant articles and documents
Synthesis, microbial transformation, and pharmacological evaluation of 4,5-dihydronaphtho[2,1-b]furan-2-ones and related analogues
El Sayed, Khalid A.,Foudah, Ahmed I.,Mayer, Alejandro M. S.,Crider, A. Michael,Song, Daniel
, p. 1231 - 1238 (2013)
Reaction of 5- or 7-methoxy-2-tetralone with an α-bromoester using lithium diisopropylamide as the base gave tricyclic naphtho[2,1-b]furan-2-ones in one step. Catalytic reduction, epimerization with triethylamine and microbial transformations yielded seve
Optimization of (phenylmethylidene)-hydantoins as prostate cancer migration inhibitors: SAR-directed design, synthesis, and pharmacophore modeling
Mudit, Mudit,El Sayed, Khalid A.
experimental part, p. 1470 - 1485 (2011/11/06)
Prostate cancer is one of the most common cancer forms among males of Western countries. Natural products proved to be an unparalleled source of molecular diversity. The 4-(hydroxyphenylmethylidene)hydantoin (PMH; 1), (5Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione, was isolated from the Red Sea sponge Hemimycale arabica, and recently showed junctional complexes stabilization, anti-invasive, and antimetastatic activities in vitro and in vivo. The related synthetic analogue, (5Z)-5-[4-(ethylsulfanyl)benzylidene] imidazolidine-2,4-dione (2), showed several-fold-improved in vivo antimetastatic properties against the highly invasive prostate cancer. To further optimize the activity of PMHs, various ligand-based strategies were used including the extension of the structure, structural simplification, linker extension, and computer-assisted CoMFA (Comparative Molecular Field Analysis) results. These strategies yielded thirty 2nd-generation PMHs, designed based on the 1st-generation PMHs, such as 1 and 2. Wound-healing assay was selected to evaluate the in vitro anti-migratory potential of these new PMHs against the PC-3 cell line. Several active PMHs, including 10, 13, 24, 29, with nearly twelvefold enhancement of activity vs. 2, were identified. Active compounds were then used to build a pharmacophore model using the SYBYL's DIStance COmparison technique (DISCOtech). Active PMHs were also screened for fragment-based drug likeness using the OSIRIS program, and an overall drug score was also calculated. Interestingly, the overall drug scores of 24 and 29 along with their anti-migratory activity were significantly greater than those of 1 and 2. In conclusion, PMHs can be the appropriate scaffolds for the urgently needed drug candidates for the control of androgen independent prostate cancer. Copyright
Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products
Mudit, Mudit,Khanfar, Mohammad,Muralidharan, Anbalagan,Thomas, Shibu,Shah, Girish V.,van Soest, Rob W.M.,El Sayed, Khalid A.
experimental part, p. 1731 - 1738 (2009/08/07)
The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl)hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the sy
The marine natural-derived inhibitors of glycogen synthase kinase-3β phenylmethylene hydantoins: In vitro and in vivo activities and pharmacophore modeling
Khanfar, Mohammad A.,Asal, Bilal Abu,Mudit, Mudit,Kaddoumi, Amal,El Sayed, Khalid A.
experimental part, p. 6032 - 6039 (2009/12/06)
The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1). This natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)-hydantoin (2) showed potent in vitro and in vivo anti-gr
