1226993-16-3Relevant academic research and scientific papers
Biological evaluation of synthetic analogues of curcumin: Chloro-substituted-20-hydroxychalcones as potential inhibitors of tubulin polymerization and cell proliferation
Aryapour, Hassan,Riazi, Gholam Hossein,Foroumadi, Alireza,Ahmadian, Shahin,Shafiee, Abbas,Karima, Oveis,Mahdavi, Majid,Emami, Saeed,Sorkhi, Maedeh,Khodadady, Sirus
, p. 503 - 510 (2011)
A series of chloro-substituted-20-hydroxychalcones were prepared and evaluated for their cytotoxic effects against K562 and SK-N-MC human cancer cell lines and as the inhibitors of tubulin polymerization. The 3,50-dichloro- analogue (compound 3) inhibited the assembly of protofilaments with 89% inhibition. Compound 3 was found to be bound to tubulin with a dissociation constant of 3.7 lM and altered far-UV circular dichroism spectrum of tubulin and altered far-UV circular dichroism spectrum of tubulin.
Multitarget 2′-hydroxychalcones as potential drugs for the treatment of neurodegenerative disorders and their comorbidities
?akelj, Simon,Abin-Carriquiry, Juan Andrés,Carvalho, Diego,Colettis, Natalia,Gobec, Stanislav,Higgs, Josefina,Kamecki, Fabiola,Knez, Damijan,Marcos, Alejandra,Marcucci, Carolina,Marder, Mariel,Rademacher, Marina,de Tezanos Pinto, Felicitas
, (2021/10/19)
The complex nature of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD) calls for multidirectional treatment. Restoring neurotransmitter levels by combined inhibition of cholinesterases (ChEs) and monoamine oxidases (MAOs, MAO-A and MAO-B), in conjunction with strategies to counteract amyloid β (Aβ) aggregation, may constitute a therapeutically strong multi-target approach for the treatment of NDDs. Chalcones are a subgroup of flavonoids with a broad spectrum of biological activity. We report here the synthesis of 2′-hydroxychalcones as MAO-A and MAO-B inhibitors. Compounds 5c (IC50 = 0.031 ± 0.001 μM), 5a (IC50 = 0.084 ± 0.003 μM), 2c (IC50 = 0.095 ± 0.019 μM) and 2a (IC50 = 0.111 ± 0.006 μM) were the most potent, selective and reversible inhibitors of human (h)MAO-B isoform. hMAO-B inhibitors 1a, 2a and 5a also inhibited murine MAO-B in vivo in mouse brain homogenates. Molecular modelling rationalised the binding mode of 2′-hydroxychalcones in the active site of hMAO-B. Additionally, several derivatives inhibited murine acetylcholinesterase (mAChE) (IC50 values from 4.37 ± 0.83 μM to 15.17 ± 6.03 μM) and reduced the aggregation propensity of Aβ. Moreover, some derivatives bound to the benzodiazepine binding site (BDZ-bs) of the γ-aminobutyric acid A (GABAA) receptors (1a and 2a with Ki = 4.9 ± 1.1 μM and 5.0 ± 1.1 μM, respectively), and exerted sedative and/or anxiolytic like effects on mice. The biological results reported here on 2′-hydroxychalcones provide an extension to previous studies on chalcone scaffold and show them as a potential treatment strategy for NDDs and their associated comorbidities.
