136054-85-8Relevant articles and documents
Spectroscopic analysis by NMR, FT-Raman, ATR-FTIR, and UV-Vis, evaluation of antimicrobial activity, and in silico studies of chalcones derived from 2-hydroxyacetophenone
Xavier, Jayze da Cunha,de Almeida-Neto, Francisco W.Q.,Rocha, Janaína E.,Freitas, Thiago S.,Freitas, Priscila R.,de Araújo, Ana C.J.,da Silva, Priscila T.,Nogueira, Carlos E.S.,Bandeira, Paulo N.,Marinho, Márcia M.,Marinho, Emmanuel S.,Kumar, Nitin,Barreto, Ant?nio C.H.,Coutinho, Henrique D.M.,Juli?o, Murilo S.S.,dos Santos, Hélcio S.,Teixeira, Alexandre M.R.
, (2021/05/31)
Six 2’-hydroxychalcones were synthesized and characterized by NMR, FT-Raman, ATR-FTIR, and UV-Vis. These chalcones alone and in combination with the ciprofloxacin, penicillin, and erythromycin antibiotics were tested against multiresistant strains of Staphylococcus aureus. It was also verified by in vitro and in silico studeis the capacity of these chalcones to inhibit the NorA efflux pump. The MICs values of ciprofloxacin were reduced in the presence of all tested chalcones. For norfloxacin antibiotic, the chalcones A1, A4, A5 and A6 promoted the reduced in the MIC values. The A2 chalcone was the only one to reduce the MIC values when associated with penicillin. Any chalcones were not able to reduce MIC values when associated with erythromycin. These results indicate that the synergistic effects demonstrated for the synthesized chalcones were influenced by the introduction of a furanic ring (A1), a chlorine atom and a methoxy group at the C4 position (A2 and A4), a second double bond (A5), and a fluorine atom at the C2 position (A6). The ADMET analysis predicts that the chalcones A2, A3, A5 and A6 have easier cell permeation. The nucleophilic region makes the A5 chalcone capable of covalently bonding with plasma proteins, and the presence of oxygenated aromatic substitutions makes the chalcones A1 and A4 more water-soluble and consequently easier to excrete. On the other hand, the substitution of the methoxy group of the A4 chalcone makes it more susceptible to O-demethylation reactions by the CYP3A4 isoenzyme. The molecular docking revealed that all six chalcones could hinder the binding of norfloxacin to the NorA efflux pump.
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.
2′-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole
Alves, Mirna Samara Dié,Borsuk, Sibele,Casaril, Angela Maria,Ramos, Daniela Fernandes,Savegnago, Lucielli,Sena-Lopes, ?ngela,da Rocha Fonseca, Bárbara,da Silva, Caroline Carapina,das Neves, Raquel Nascimento,de Pereira, Claudio Martin Pereira
, (2019/12/27)
The treatment for trichomoniasis, based on 5′-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates. There are no alternative drugs approved for the treatment of these cases; thus, the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities. Here, we presented the synthesis of three hydroxychalcones (3a, b, and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12?h of incubation at minimum inhibitory concentration (MIC) of 100?μM. 3c showed a dose-dependent cytotoxicity against mammalian VERO cell line, but the association of 3c at 12.5?μM and metronidazole (MTZ) at 40?μM showed 95.31% activity against T. vaginalis trophozoites after 24?h of exposure and did not affect the VERO cell growth, appearing to be a good alternative. In silico analysis by molecular docking showed that 3c could inhibit the activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase), and TvPNP (purine nucleoside phosphorylase) affecting the T. vaginalis survival and also suggesting a different mechanism of action from MTZ. Therefore, these results propose that hydroxychalcones are promising anti-T. vaginalis agents and must be considered for further investigations regarding trichomoniasis treatment.
