49 research outputs found
3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different
substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of
colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812
and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically
expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally
affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase
inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing
G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in
human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML
Palladium-Catalyzed Cross-Coupling Reaction of Allyl Acetates with Pinacol Aryl- and Vinylboronates
An Efficient Synthesis of 4-Aryl and 4-Vinylphenylalanines by Stille Cross-Coupling Reaction
A Convenient Preparation of Selectively Protected L-DOPA derivatives from 3-iodo-L-Tyrosine
Discussion Addendum for: Palladium-Catalyzed Reduction of Vinyl Trifluoromethanesulfonates to Alkenes: Cholesta-3,5-DieneOrganic Syntheses
cholesta-3,5-diene
2,6-lutidine
1,1’-bis(diphenylphosphino)ferrocene
1,3-bis(diphenylphosphino)propane
1,3-bis(diphenylphosphino)butane
Pinacolborane
3-methyl-1-azatricyclo[5.2.1.0]decane
(–)-Galantamin
Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold
A series of (1H-benzo[d][1,2,3]triazol-1-yl)(4-benzylpiperazin-1-yl) methanones and of (1H-benzo[d][1,2,3]triazol-1-yl)(4-phenylpiperazin-1-yl) methanones has been prepared and tested on human fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). In the benzylpiperazinyl series, compound 29 (ML30) exhibited an IC50 value of 0.54 nM on MAGL, combined with a 1000-fold selectivity versus FAAH, while compounds 11 and 16 acted as potent dual FAAH-MAGL inhibitors (IC50 <10 nM). In the phenylpiperazinyl series, compounds 37, 38, 42, and 43 displayed IC50 values against MAGL in the nanomolar range, whilst being between one and two orders of magnitude less potent on the FAAH, while compounds 31 and 32 were potent FAAH inhibitors (IC50 <20 nM) and over 12-fold selective versus MAGL. The key structural determinants driving the structure-activity relationships were explored by the minimization of the inhibitors inside the active site of both enzymes. © 2012 Elsevier Ltd. All rights reserved