1542744-03-5Relevant academic research and scientific papers
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors
Loh, Zi Han,Kwong, Huey Chong,Lam, Kok Wai,Teh, Soek Sin,Ee, Gwendoline Cheng Lian,Quah, Ching Kheng,Ho, Anthony Siong Hock,Mah, Siau Hui
, p. 627 - 639 (2021/02/16)
A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 μM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π–π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π–π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.
New chiral derivatives of xanthones: Synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines
Fernandes, Carla,Masawang, Kamonporn,Tiritan, Maria Elizabeth,Sousa, Emília,De Lima, Virgínia,Afonso, Carlos,Bousbaa, Hassan,Sudprasert, Wanwisa,Pedro, Madalena,Pinto, Madalena M.
, p. 1049 - 1062 (2014/02/14)
A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed According to this approach, thirty CDXs (3-32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building blocks, namely six amino alcohols, one amine and one amino ester The activation of the carboxylic acid group of the xanthonic scaffold was carried out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N′-N′-tetramethyluronium tetrafluoroborate (TBTU), in the presence of a catalytic amount of TEA in anhydrous THF The coupling reactions with the chiral blocks were performed at room temperature with short reactions times, excellent yields (ranging from 94% to 99%), and very high enantiomeric excess The synthesized CDXs were evaluated for their effect on the in vitro growth of three human tumor cell lines, namely A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer) The most active compound was CDX 15 being active in all human tumor cell lines with values of GI50 of 32.15 ± 2.03 μM for A375-C5, 22.55 ± 1.99 μM for MCF-7, and 14.05 ± 1.82 μM for NCI-H460 Nevertheless, some CDXs showed cell-type selectivity Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs An interesting example was observed with the enantiomers 3 and 4, which demonstrated high enantioselectivity for MCF-7 and NCI-H460 cell lines It can be inferred that the effects on the growth of the human tumor cell lines can be ascribed not only to the nature and positions of substituents on the xanthonic scaffold but also to the stereochemistry of the CDXs Some considerations regarding structure-activity relationship within this class of compounds will be highlighted
