252006-47-6Relevant academic research and scientific papers
Small multitarget molecules incorporating the enone moiety
Liargkova, Thalia,Eleftheriadis, Nikolaos,Dekker, Frank,Voulgari, Efstathia,Avgoustakis, Constantinos,Sagnou, Marina,Mavroidi, Barbara,Pelecanou, Maria,Hadjipavlou-Litina, Dimitra
, (2019/01/21)
Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 μM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 ?) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.
Difunctional Heterocycles: A Convenient Synthesis of Bis(4,5-dihydropyrazolyl) ethers from Their Precursors Bis(chalcones)
Elwahy, Ahmed H. M.
, p. 2582 - 2596 (2007/10/03)
The new bis(4,5-dihydropyrazolyl)ethers 18-22, 26, 27 and 40-44 were prepared in 30-80 percent yields by condensation of the corresponding bis(chalcones) 13-17 and 34-37 with each of hydrazine and phenylhydrazine. Attemptes to prepare compound 20 by alkylation of 24 with 1,4-dibromobutane were unsuccessful and instead the monoalkylated derivatives 25 was obtained in 45 percent yield. Compound 24 was obtained in 63 percent yield by reacting 23 with hydrazine hydrate in refluxing acetic acid. The bis(chalcones) 13-17 and 34-37 were obtained in 65-80 percent yields by basic condensation of each of the bis(acetyl) derivatives 8-12 and the bis(aldehyde) derivatives 30-33 with benzaldehyde and acetophenone respectively. Compounds 14, 15, 35 and 36 were alternatively obtained in 32-44 percent yields by alkylation of each of the 4-cinnamoylphenol 23 and 4-benzoylvinylphenol 38 with the appropriate dibromoalkane.
